Diabetic wounds can experience dysregulated inflammation and impaired progression through the inflammatory, proliferative and remodeling stages of healing. Mesenchymal stem cells have regenerative and paracrine potential, but their function may be compromised within the diabetic wound microenvironment. The study investigated whether factors associated with a particular stage of normal wound repair could condition the cells before they were introduced into diabetic wounds. The investigators isolated and characterized bone marrow-derived mesenchymal stem cells, evaluated extracts from normal and diabetic rat wounds, and used the 10 µg/mL concentration because it did not kill the cells during conditioning.

Scratch assays showed that N9-conditioned mesenchymal stem cells enhanced wound closure in vitro. In contrast, cells conditioned with diabetic day-9 wound extract, designated D9, had elevated expression of inflammatory genes and reduced expression of angiogenic and proliferative markers. These measurements indicate that day-9 extracts from normal and diabetic wounds exerted different molecular effects on the conditioned cells. The findings do not isolate which individual proteins were responsible for those effects or establish how the factor mixture acted over time.

In the diabetic wound transplantation model, N9-conditioned mesenchymal stem cells significantly accelerated wound closure compared with the experimental controls. Histological analysis using hematoxylin and eosin staining indicated restoration of tissue architecture and improved collagen organization. Immunofluorescence for α-smooth muscle actin, or α-SMA, showed an increased number of α-SMA-positive vascular structures, supporting enhanced vascular remodeling in the treated wounds. These observations provide evidence that the normal day-9 extract improved several measured outcomes in diabetic wound repair, although the experiments involved cultured cells and rats rather than people with diabetes.

The study therefore supports phase-specific wound-derived factors as a means of changing mesenchymal stem-cell behavior before transplantation. Its strongest result is that conditioning with N9 produced cells with greater wound-closure activity in vitro and improved closure, tissue structure, collagen organization and α-SMA-positive vascular structures in the rat model. The evidence does not demonstrate clinical benefit in human diabetic wounds, and no human trial was reported. The results offer a preclinical basis for further studying wound-derived protein factors in cell-based repair, while the contribution of individual factors and the relevance of the strategy across settings remain unresolved.

Subject of Research: Preclinical testing of remodeling-phase wound factors and mesenchymal stem cells in diabetic wound repair

Article Title: Remodeling-phase wound-derived protein factors enhance mesenchymal stem cell function and improve diabetic wound healing

Article References: Zaidi, M. B., Aslam, S., Jameel, F., Khan, I., & Salim, A. (2026). Remodeling-phase wound-derived protein factors enhance mesenchymal stem cell function and improve diabetic wound healing. Molecular Biology Reports, 53(1), Article 1515. https://doi.org/10.1007/s11033-026-12706-w

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12706-w

Keywords: mesenchymal stem cells, diabetic wounds, wound healing, tissue remodeling, cell conditioning, vascular remodeling, protein factors, rat model, regenerative medicine, Remodeling-phase, wound-derived, protein

The research team, co-led by Francesca Duncan, associate professor of reproductive science in medicine at Northwestern University Feinberg School of Medicine, and Birgit Schilling, professor and director of the Mass Spectrometry Center at the Buck Institute, set out to do something deceptively simple: look closely at what postmenopausal ovarian tissue is actually doing at the molecular level. Duncan herself admits she expected to find very little. “In the ovary, we reach a point of no return with respect to fertility in which it’s no longer producing eggs, and I would venture to say most people assume those ovaries are just sitting there doing nothing, similar to the appendix,” she said. “But that’s what makes this study very different.” Her initial prediction was that ovaries taken from 50-, 60-, 70- and 80-year-old women would all look essentially identical — egg-free and functionally dormant.

That prediction turned out to be wrong. To interrogate the tissue, the scientists moved beyond the hormones that have traditionally dominated ovarian research and instead analyzed the organ’s full protein composition at high resolution. Using advanced proteomic technologies paired with mass spectrometry — approaches capable of identifying and quantifying thousands of proteins simultaneously — Schilling’s team, spearheaded by staff scientist Mark Watson, profiled 5,812 protein groups in normal ovarian tissue from postmenopausal women between the ages of 50 and 75. This large-scale molecular census allowed the researchers to track how protein abundance shifts across the postmenopausal decades and to search for consistent patterns using multiple types of statistical analysis, rather than relying on any single analytical lens.

The picture that emerged was remarkably coherent. Ovaries from younger postmenopausal women carried a heavier complement of proteins involved in maintaining cells and tissue structure, while ovaries from older women showed increasing levels of proteins associated with inflammation, immune activity, and the ongoing breakdown and rebuilding of the extracellular matrix — the scaffolding that surrounds cells. The molecular differences were most pronounced when the researchers compared ovaries from women in their 50s with those from women aged 70 and older. “When we analyzed the data in multiple different statistical ways, what became clear across all these methodologies is that the ovary was not stagnant,” Schilling said. “In fact, over the decades, there were quite dramatic differences in terms of some proteins’ levels would go up with age and some proteins’ levels would go down, which tells us this organ is quite dynamic.”

The aging ovaries also displayed molecular signatures associated with cellular senescence, a state in which aging or damaged cells stop dividing but remain biologically active, secreting inflammatory signals and other molecules that can influence surrounding tissue. Senescent cells have been implicated in a wide range of age-related conditions, and their presence in postmenopausal ovarian tissue adds the ovary to the growing list of organs that appear to accumulate these problematic cell states over time. Taken together, the findings point to what Duncan describes as progressive aging features, in which the ovary seems to gradually lose its original reproductive identity and take on an altogether different biological character.

Human ovarian tissue is notoriously difficult to obtain, which makes the 28 ovaries in this study an unusually valuable scientific resource. The design of the research also matters: rather than comparing young ovaries with old ones across the entire human lifespan — an approach that inevitably conflates pre- and postmenopausal biology — the team deliberately focused on women within a relatively narrow 25-year age window after menopause. This strategy allowed them to isolate molecular changes that continue to unfold specifically during the postmenopausal years, a period of life that has expanded dramatically as women now routinely live for decades beyond the end of their reproductive capacity. Duncan’s group had previously documented similar continued remodeling in the postmenopausal ovaries of mice, and she notes that seeing the same phenomenon across species lends confidence that what they are observing is not a random artifact but a meaningful feature of ovarian biology.

Perhaps the most provocative finding concerns cancer. More than a decade ago, Duncan’s lab was the first to show that as ovaries age, they become increasingly inflamed, fibrotic and stiff — a process resembling scarring in other tissues. Because cancer cells are known to thrive in collagen-rich, stiff environments, her team has long investigated whether such age-related changes might make the ovary more hospitable to malignant cells. The new study offers a molecular view of that same remodeling process later in life: as postmenopausal ovaries aged, structural proteins declined while inflammation-related and tissue-reshaping proteins became more prominent. Although every tissue sample in the study appeared normal and cancer-free, several proteins previously linked to ovarian cancer were more abundant in the aging ovaries, with the strongest signal observed among women in their 60s. The researchers stress this does not mean the ovaries were cancerous or precancerous — only that healthy ovarian aging and ovarian cancer appear to share some of the same underlying biological processes.

Duncan frames the observation in terms of a broader model of cancer development. “It’s not that all postmenopausal women get ovarian cancer, but we know that that fibrotic inflammatory environment is certainly an environment that cancer cells prefer to home in on,” she said. “This is all consistent with the idea that the aging ovary is a potential third hit for ovarian cancer, with the first hit being genetic and the second hit being environmental. So can we target the aging ovary therapeutically to lower the risk of ovarian cancer, or can we develop novel biomarkers of ovarian cancer?” If the aging ovary’s microenvironment does indeed lower the barrier to malignancy, it could open entirely new avenues for prevention — from anti-inflammatory or anti-fibrotic interventions to early-detection markers rooted in the protein changes the study catalogued.

The work also raises a question that few clinicians have had reason to ask: should otherwise healthy ovaries ever be removed after menopause? “The ovary is not just a reproductive organ,” Schilling said. “It really influences how somebody ages because it speaks to all these other organs, such as the brain, and also to the bone, and women after menopause experience often a lot of bone problems. So, we think there is a connection between all these organs.” Duncan puts the stakes even more bluntly, asking whether the ovary might be “the canary in the coal mine in women” — an organ whose aging could set off a cascade of changes throughout the body. Much remains unknown, including whether the postmenopausal ovary’s activity is beneficial or harmful, and whether there is ever a point at which the organ stops helping and starts hurting. “Our data points to progressive aging features in which the ovary appears to lose its original identity and ends up doing something different,” Duncan said. “We do not yet know if there’s ever a point in a woman’s life when this organ is no longer beneficial and it’s actually harmful. These results really point to the need to ask this question.” The researchers emphasize that their findings do not answer whether healthy ovaries should be removed; instead, they open a new frontier of research into how this long-ignored organ shapes women’s health in the decades after reproduction ends.

Subject of Research: Molecular remodeling of the human ovary in the decades after menopause

Article Title: The ovary doesn’t retire after menopause

Article References: The ovary doesn’t retire after menopause. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: ovary, menopause, aging, proteomics, inflammation, fibrosis, ovarian cancer, cellular senescence, tissue remodeling, Northwestern University, Buck Institute, Aging Cell

The team, led by Shilong Liu and senior author Zhenhua Zhu of the First Affiliated Hospital of Hunan University of Chinese Medicine, began by mining publicly available single-cell RNA sequencing datasets from the Gene Expression Omnibus. After quality control and integration, they analyzed 41 CRSwNP samples and 7 healthy controls, resolving the nasal tissue microenvironment into 13 major cell populations. They then zoomed in on the two compartments most directly responsible for tissue architecture: the epithelium, which forms the mucosal barrier, and the fibroblasts of the underlying lamina propria, which manufacture the extracellular matrix. Epithelial cells resolved into 13 subpopulations and fibroblasts into 8, each defined by distinct functional states.

The compositional shifts they observed were striking and asymmetric. In the epithelial compartment, six of the thirteen subpopulations changed significantly in disease. Inflammatory CXCL8-positive cells and MUC5AC-positive goblet cells expanded, while homeostatic FOXJ1-positive ciliated cells, the workhorses of mucociliary clearance, shrank. Basal-like populations marked by KRT15 and COL17A1 grew, signaling a tissue locked into a perpetual injury-repair mode. Fibroblasts shifted more modestly, but the direction was telling: inflammatory CCL2-positive fibroblasts increased while APOD-positive homeostatic fibroblasts declined. The epithelium, in other words, tilted toward inflammation and aberrant secretion, while the stroma edged toward activation.

Differential expression and gene set enrichment analysis deepened the story. Diseased epithelial cells upregulated genes tied to injury responses and remodeling, including SERPINB4, KRT13, MMP7, and VIM, while losing genes that maintain barrier function and ciliary differentiation such as SCGB1A1, FOXJ1, and MUC5B. Enriched pathways included epithelial-mesenchymal transition, hypoxia, inflammatory response, and TGF-beta and WNT signaling. Fibroblasts showed a complementary profile: POSTN, COL1A2, SERPINE1, and CCL2 rose, while homeostatic genes like PI16 and MFAP4 fell, with collagen metabolism and TGF-beta production prominently enriched. Shared hub genes such as IL6 and SERPINE1 appeared in both cell types, hinting at a common inflammatory and matrix-remodeling program.

Pseudotime analysis using Monocle3 and CytoTRACE2 then reconstructed how these states emerge. Epithelial cells appeared to branch from a secretory starting point toward ciliated, mucous, and injury-repair fates, with homeostatic genes like EPCAM and CDH1 declining along the trajectory while KRT15, COL17A1, and the EMT-associated transcription factor SNAI2 increased. Fibroblasts progressed from quiescent CFD- and APOD-expressing states toward activated, contractile phenotypes marked by TAGLN, POSTN, and MYL9, with collagen genes COL1A1 and COL1A2 peaking in mid-to-late pseudotime. The picture is one of gradual, coordinated drift away from tissue homeostasis rather than an abrupt switch.

The most consequential findings came from CellChat, a computational framework that infers ligand-receptor communication between cell populations. In CRSwNP, the overall communication network grew denser and stronger, with two modules standing out. The COLLAGEN module, built on pairs such as COL1A1 and COL1A2 binding CD44, SDC4, and integrins, flowed predominantly from activated fibroblast subpopulations toward specific epithelial subsets. The TGF-beta module, involving TGFB1 binding TGFBR1/TGFBR2 and ACVR1, was more bidirectional, with epithelial and fibroblast compartments signaling reciprocally. Extending the analysis to myeloid cells, the team found that TGFB1 transcripts concentrated in a GPNMB-expressing macrophage state, marked by SPP1, TREM2, and MMP9, that was significantly expanded in polyps, echoing scar-associated macrophages described in fibrotic liver and other tissues.

Crucially, the computational predictions held up at the protein level in human tissue. Examining nasal polyps from three patients and control mucosa from three individuals undergoing septal surgery, the researchers used Masson’s trichrome staining and tyramide signal-amplified immunofluorescence. Polyps showed denser subepithelial collagen deposition, stronger COL1A1 and alpha-SMA signals in the lamina propria, nuclear accumulation of phosphorylated Smad3 in epithelial cells, weakened E-cadherin, and increased N-cadherin and periostin, all statistically significant. One particularly revealing observation concerned architecture rather than abundance: in healthy mucosa, COL1A1 and periostin formed a compact, continuous band beneath the epithelium, but in polyps this band became loose and discontinuous, with matrix proteins diffusing into the lamina propria. Remodeling in CRSwNP, the data suggest, involves not just more matrix but disorganized matrix.

To test causality in a living system, the team established a CRSwNP-like mouse model using intranasal ovalbumin challenge combined with Staphylococcus aureus enterotoxin B, a superantigen long implicated in polyp formation. Over roughly four months, model mice developed thickened respiratory epithelium, polypoid protrusions, inflammatory infiltration, and significantly increased subepithelial collagen by Sirius Red staining under polarized light. Immunofluorescence mirrored the human findings: alpha-SMA-positive cells accumulated with COL1A1 deposition, epithelial E-cadherin fell, nuclear p-Smad3 rose, and N-cadherin and periostin increased. Western blotting confirmed elevated COL1A1, POSTN, N-cadherin, alpha-SMA, and an increased p-Smad3 to total Smad3 ratio.

The therapeutic implications emerged when the researchers treated model mice with dexamethasone, the corticosteroid that remains first-line therapy for CRSwNP. The drug partially reversed the remodeling phenotype: alpha-SMA and E-cadherin returned to levels statistically indistinguishable from controls, while COL1A1, POSTN, and N-cadherin declined but stayed above baseline. The p-Smad3/Smad3 ratio showed only a non-significant downward trend. This partial response is mechanistically coherent, since the glucocorticoid receptor is known to directly inhibit the transcriptional activation function of Smad3, but it also carries a sobering message: broad anti-inflammatory treatment alone may not fully reverse established structural remodeling, and pathway-targeted anti-fibrotic strategies deserve exploration.

The authors are careful about the limits of their work. CellChat and pseudotime analyses are computational inferences that nominate candidate signaling axes rather than prove physical ligand-receptor engagement, and no knockdown, pathway blockade, or co-culture experiments were performed. The two public cohorts differ in ethnicity and inflammatory endotype, one skewed toward Type 2 inflammation and the other toward IL-1beta-driven myeloid inflammation, and eosinophils, classic sources of TGF-beta1 in polyps, were too sparsely captured for subcluster analysis. Yet the reproducible detection of the same epithelial-fibroblast TGF-beta/Smad axis across cohorts differing in platform, ancestry, and sampling site argues that it is a shared feature of polyp remodeling rather than a cohort-specific artifact. If future spatially resolved and functional studies confirm this circuit, the collagen and TGF-beta dialogue between epithelium and stroma could become a tractable target for therapies aimed not just at shrinking polyps, but at preventing the scarring that makes them return.

Subject of Research: TGF-beta/Smad-mediated epithelial-fibroblast remodeling and collagen deposition in chronic rhinosinusitis with nasal polyps

Article Title: TGF‐β/Smad‐Associated Epithelial–Fibroblast Remodeling Underlies Collagen Deposition in Chronic Rhinosinusitis With Nasal Polyps

Article References: Liu, S., Xie, P., Deng, H., & Zhu, Z. (2026). TGF‐β/Smad‐Associated Epithelial–Fibroblast Remodeling Underlies Collagen Deposition in Chronic Rhinosinusitis With Nasal Polyps. Immunity, Inflammation and Disease, 14(10), Article e70532. https://doi.org/10.1002/iid3.70532

Image Credits: AI Generated

DOI: 10.1002/iid3.70532

Keywords: chronic rhinosinusitis, nasal polyps, TGF-beta, Smad3, fibroblasts, epithelial-mesenchymal transition, collagen deposition, single-cell RNA sequencing, CellChat, macrophages, dexamethasone, tissue remodeling

BPH is not cancer, but it is hardly a minor inconvenience. The noncancerous overgrowth of prostate cells becomes increasingly common as men age, and as the gland swells it can compress the urethra, the narrow tube that carries urine out of the body. The consequences are familiar to millions of older men: frequent urination, repeated nighttime trips to the bathroom, a weak urinary stream, and the frustrating sensation that the bladder never fully empties. Despite how widespread the condition is, the biological events that set it in motion — and in particular the question of why it arises almost exclusively in one region of the prostate — have remained stubbornly unresolved. Senior author Vasan Yegnasubramanian, a professor of oncology, pathology, and radiation oncology and molecular radiation sciences at the Johns Hopkins Kimmel Cancer Center and director of inHealth Precision Medicine at Johns Hopkins Medicine, noted that although BPH affects millions of men worldwide, scientists still do not fully understand why it develops primarily in the transition zone while other regions of the gland remain relatively unaffected.

That regional puzzle is rooted in the prostate’s internal architecture. The gland is not a uniform organ but is divided into several anatomically and biologically distinct compartments, most notably the peripheral zone, the central zone, and the transition zone. These regions differ in their cellular makeup and in their vulnerability to disease, and the split is dramatic: BPH arises almost exclusively in the transition zone, the area surrounding the urethra, while the majority of prostate cancers emerge in the peripheral zone. Understanding why the same organ hosts two such different disease patterns has long been a goal of prostate biology, and it suggests that the answer lies in fundamental differences in the cells that populate each zone.

To pursue that question at single-cell resolution, the research team, led by Yegnasubramanian together with Rulin Wang, a research associate and the study’s first author, and Angelo De Marzo, professor of pathology at the Johns Hopkins University School of Medicine and associate director of cancer research pathology at the Kimmel Cancer Center, turned to single-cell RNA sequencing. This technology allows investigators to determine which genes are switched on or off in individual cells, rather than averaging signals across a bulk sample in which rare cell types can vanish into the noise. The team studied noncancerous prostate tissue collected from 10 men undergoing surgery for localized prostate cancer, obtaining samples from all three major zones of the gland and profiling gene expression in nearly 130,000 individual cells.

The first task was cartographic: identifying the major cell types present throughout the prostate and confirming how they were distributed across zones. With that atlas in hand, the researchers zoomed in on basal epithelial cells, a population that helps form the lining of the prostate and is thought to include progenitor-like cells capable of contributing to tissue maintenance and repair. Rather than finding a single homogeneous basal population, the analysis revealed that these cells split into four distinct molecular subtypes — a level of diversity that conventional histology had not exposed.

One of those four subtypes immediately stood out. Its cells expressed high levels of a gene called WIF1, along with several other genes, and their distribution across the gland was anything but random. Additional laboratory tests confirmed that these WIF1-positive basal cells were abundant in the transition zone but nearly absent from the peripheral and central zones. In other words, the researchers had found a cell population whose geographic footprint within the prostate matched, almost exactly, the territory where BPH takes hold.

The molecular profile of these cells offered further clues about what they might be doing. According to Wang, the analysis revealed that the cells possess molecular features associated with tissue remodeling that could contribute to prostate enlargement, as well as an ability to communicate with neighboring cells, suggesting they may help establish the unique biological environment of the transition zone. Tissue remodeling — the orchestrated breakdown and rebuilding of structural components — is a normal part of organ maintenance, but when it runs unchecked it can drive the kind of nodular overgrowth seen in BPH. A cell type equipped with remodeling programs and embedded in the exact region where that overgrowth occurs is a compelling candidate for a local driver of the disease process.

Perhaps most tellingly, the team found that WIF1-positive basal cells are expanded in BPH tissues. That expansion raises the possibility, the researchers say, that these cells contribute to the regional processes that make the transition zone particularly susceptible to BPH. The gene whose name the cells carry, WIF1, encodes a Wnt inhibitory factor, a secreted molecule that modulates Wnt signaling — a pathway with well-established roles in development, stem cell behavior, and tissue growth. The presence of a Wnt-pathway regulator in a remodeling-competent basal population enriched at the BPH epicenter suggests a plausible mechanism by which local signaling environments could shape where and how the gland enlarges, though the study’s authors frame this as a foundation for future work rather than a settled causal story.

The significance of the finding lies less in any single gene than in the strategy it validates. Bulk analyses of prostate tissue have long averaged together the signals of many cell types, obscuring the rare, regionally restricted populations that may hold the key to zonal disease patterns. By dissecting the gland zone by zone at single-cell resolution, the Hopkins team showed that the transition zone carries its own distinctive cellular identity, embodied in a basal cell subtype found almost nowhere else in the organ. That identity, the researchers suggest, may be what renders the transition zone uniquely prone to the proliferative and remodeling processes of BPH — and, by extension, may help explain why the peripheral zone instead becomes the favored soil for prostate cancer.

By uncovering this distinct cell population associated with the region where BPH begins, the research provides new insight into the cellular mechanisms underlying prostate growth and remodeling, and it offers a foundation for future studies aimed at understanding how the condition develops. The long-term hope, the researchers say, is that a clearer picture of the transition zone’s biology will ultimately support more precise ways to prevent, diagnose, and treat BPH — potentially allowing therapies that target the specific cell programs driving enlargement rather than broadly suppressing prostate growth. The study also involved contributions from Qizhi Zheng, Mindy Graham, Ajay Vaghasia, Jianyong Liu, Jordan Gregg, Tracy Jones, Anuj Gupta, Nicole Castagna, Yan Zhang, Kornel Schuebel, Jennifer Meyers, Alyza Skaist, Dixie Hoyle, Jasmine Kung, Jessica Hicks, Alok Mishra, Yuhan Yang, and William Nelson. The work was supported by the National Institutes of Health and the National Cancer Institute, the Prostate Cancer Foundation, and several philanthropic and institutional funds, including the Patrick G. Walsh Fund and the Maryland Cigarette Restitution Fund.

Subject of Research: Identification of a WIF1-positive basal epithelial cell type in the prostate transition zone associated with benign prostatic hyperplasia

Article Title: Newly identified prostate cell type may help explain why enlarged prostate develops in one region of gland

Article References: Newly identified prostate cell type may help explain why enlarged prostate develops in one region of gland. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: benign prostatic hyperplasia, prostate, transition zone, basal epithelial cells, WIF1, single-cell RNA sequencing, Johns Hopkins, tissue remodeling, prostate zones, urology, aging, cell biology

The research, led by Mari Tolonen, Ziwei Xu, and Jakub Sedzinski of the University of Copenhagen together with Bianca Dumitrascu’s group at Columbia University, tackled a problem that has long frustrated developmental biologists: how to quantify the behavior of thousands of individual cells inside a densely packed, actively remodeling tissue. Morphology is often treated as a downstream consequence of fate decisions, a passive readout of the genetic program. The team set out to test a bolder idea, namely that the dynamic geometry of a cell might serve as a complementary, and potentially predictive, indicator of its state, in the same way that transcriptomic profiles define molecular identity.

Their experimental system was the Xenopus mucociliary epithelium, a bilayered embryonic skin that closely resembles the cellular composition of the mammalian airway. The researchers dissected animal cap explants from embryos at early blastula stages, when the tissue was still multipotent, and mounted them on fibronectin-coated dishes where they flattened into stratified epithelia amenable to long-term optical access. Embryos had been injected with messenger RNAs encoding membrane-localized mNeonGreen and nuclear H2B-RFP, allowing both cell boundaries and nuclei to be visualized. Volumetric confocal time-lapse imaging then captured the full course of differentiation, from NF stage 9 through stage 30, with z-stacks acquired every three to five minutes over 16 to 22 hours across three independent experiments.

Turning those raw movies into quantitative data required a substantial computational pipeline. Nuclei were segmented in three dimensions using a custom-trained StarDist model, while membrane signals were first denoised with a CARE network and then segmented slice by slice with Cellpose, with individual 2D contours stitched into 3D volumes based on maximal pairwise overlap. Nuclear objects were tracked over time using TrackMate, and the team integrated a convolutional neural network called Oneat to detect cell division events, which were used to impose branching points on trajectories. This combination substantially improved mitosis detection compared with TrackMate’s native algorithm, raising branching correctness from 0.122 to 0.328. On average, trajectories spanned at least 9.5 hours in a third of cells, providing sufficient temporal coverage for the analyses that followed.

From the segmentations and tracks, the researchers computed a rich set of time-resolved features for each cell: three-dimensional shape descriptors derived from point clouds resampled from surface meshes, including surface area, eccentricity, and orientation; conventional two-dimensional descriptors such as area, Feret diameter, and solidity taken from each membrane object’s central slice; nuclear shape metrics; spatial position; and instantaneous movement. The result was a high-dimensional morphodynamic feature space, conceptually analogous to a transcriptomic state vector, in which each cell’s identity at each moment was represented by dozens of quantitative measurements.

When the team explored this feature space with unsupervised methods, the picture was sobering. Principal component analysis of more than 4,200 cell trajectories revealed no distinct clusters corresponding to cell types or developmental stages. Cells were distributed continuously, with only slight shifts over time, and standard clustering metrics such as the Adjusted Rand Index and Normalized Mutual Information were uniformly low. A simple K-nearest-neighbor classifier reached a mean accuracy of just 65.8 percent against a stratified baseline of 54.0 percent, with balanced accuracy of only 28.1 percent. Unlike cultured cells, where shape heterogeneity is high and morphology alone can resolve distinct states, cells in this densely packed epithelium share constrained shapes and largely collective movement, making them hard to distinguish by any single feature.

The breakthrough came from supervised learning combined with lineage backtracking. After live imaging ended, the samples were fixed and immunostained for markers of multiciliated cells, goblet cells, small secretory cells, and basal cells, while ionocytes were identified by their characteristic morphology and lack of marker expression. By aligning the immunostained images with the final live-imaging frame, the team assigned terminal fates to roughly 75 percent of all tracked trajectories, producing a ground-truth dataset of 2,576 curated lineages. They then trained an XGBoost gradient-boosted classifier and a multinomial logistic regression model, treating each cell at each time point as an independent observation labeled by its track’s endpoint fate, with absolute experimental time included as an additional input.

The supervised models achieved moderate but consistent performance across 20 independent train-test splits. XGBoost reached a mean accuracy of 80.6 percent and a balanced accuracy of 61.4 percent, while logistic regression achieved 70.3 percent accuracy with a comparable balanced accuracy of 62.9 percent. Performance was strongest for the abundant epithelial lineages: basal cells scored an F1 of 0.90, goblet cells 0.72, and multiciliated cells 0.56 under XGBoost, whereas the rare ionocytes and small secretory cells remained difficult to classify despite class balancing with SMOTE-based oversampling and undersampling. Notably, classifier confidence and accuracy rose steadily during development, with mean confidence increasing from 0.80 at around five hours to 0.89 by 22 hours, and class-balanced accuracy climbing from 50.4 to 75.1 percent. Intriguingly, predictions for multiciliated cells peaked at roughly 15 hours, with 80.6 percent accuracy, and then declined, suggesting these cells reach a morphodynamic plateau before terminal maturation, after which their features increasingly overlap with those of goblet cells.

Feature importance analysis revealed which aspects of cellular behavior carried the predictive signal. Normalized Z position, reflecting a cell’s height within the apico-basal axis of the epithelium, was the single most informative feature, consistent with the invariant layer preferences of different lineages: goblet cells remain in the superficial layer, basal stem cells stay confined to the base, and intercalating lineages ascend. The nucleus-to-membrane centroid offset was the most predictive morphological variable in the XGBoost model, likely capturing the transition from a flat, migratory configuration to a vertically oriented shape during radial intercalation. Absolute experimental time was also a strong predictor, particularly for small secretory cells, which emerge late in development. Perhaps most strikingly, movement features contributed almost nothing to fate prediction, apparently because migration within the tissue is largely collective rather than fate-specific. Nuclear shape features proved more informative than membrane shape, which the authors attribute to the higher segmentation fidelity of nuclei.

The broader significance of this work lies in what it suggests about the nature of cell state itself. Fate, the study indicates, is not defined by discrete morphological states that cells snap into; instead, morphodynamic signatures of identity emerge gradually along continuous, overlapping trajectories, and only become legible through time-integrated, supervised analysis. Because morphodynamic tracking provides dense temporal sampling with positional context, something neither single-cell RNA sequencing nor spatial transcriptomics can fully deliver, it could complement molecular fate mapping by filling temporal and spatial gaps. The authors note that their pipeline, built from open tools including StarDist, Cellpose, TrackMate, and Oneat, can be extended to other developing tissues and combined with transcriptomics or targeted perturbations to uncover causal links between gene expression, signaling, and phenotype. Future models that incorporate neighboring cells and local tissue geometry may sharpen predictions further. For now, the message is clear: the shape a cell takes, where it sits, and when it does so are not mere consequences of its destiny but readable, quantitative clues to what that destiny will be.

Subject of Research: Machine learning prediction of cell fate from single-cell morphodynamic features during Xenopus mucociliary epithelial differentiation

Article Title: Single-cell morphodynamics predict cell fate decisions during mucociliary epithelial differentiation

Article References: Tolonen, M., Xu, Z., Beker, O., Kapoor, V., Dumitrascu, B., & Sedzinski, J. (2026). Single-cell morphodynamics predict cell fate decisions during mucociliary epithelial differentiation. Molecular Systems Biology, 22(7), 1040-1069. https://doi.org/10.1038/s44320-026-00212-x

Image Credits: AI Generated

DOI: 10.1038/s44320-026-00212-x

Keywords: cell fate, cell differentiation, Xenopus laevis, mucociliary epithelium, live imaging, morphodynamics, machine learning, XGBoost, cell tracking, segmentation, radial intercalation, developmental biology

The stroma, the connective tissue framework that surrounds and supports the milk-producing ducts and lobules of the breast, has increasingly moved from the periphery of cancer research to its center. Far from being a passive scaffold, stromal cells communicate actively with epithelial cells, secreting growth factors, remodeling the extracellular matrix, and modulating inflammation. In cancers, this crosstalk can either restrain tumor growth or fuel it. The new research asked a deceptively simple question: if reproductive events alter breast cancer risk, do they also leave detectable fingerprints in the stroma of healthy, benign tissue?

To answer it, the investigators turned to benign breast biopsy samples, a resource that captures tissue at an intermediate point—neither fully normal nor malignant. Benign breast disease itself is a well-established risk marker for subsequent breast cancer, and the composition of benign biopsies, including features such as usual ductal hyperplasia, cysts, and stromal fibrosis, has been linked to long-term risk. By examining stromal marker expression in these samples, the team sought to connect the epidemiology of reproductive factors with the microscopic biology of the tissue.

The study focused on markers that characterize distinct stromal states. Among the most important were proteins associated with fibroblast activation and extracellular matrix remodeling, including markers of myofibroblasts—the contractile, matrix-producing cells that become prominent during wound healing and are often abundant in the tissue surrounding tumors. The researchers also assessed markers reflecting the density and organization of collagen and other matrix components. Using immunohistochemical staining and quantitative pathology methods, they scored the expression of these markers across biopsy samples and then tested whether the scores varied systematically with each donor’s reproductive history.

The results revealed clear associations. Women who had never given birth showed stromal marker profiles that differed from those of parous women, consistent with the long-standing epidemiological observation that nulliparity increases breast cancer risk. Among women who had borne children, the timing of the first pregnancy emerged as a significant variable: earlier age at first full-term pregnancy was linked to stromal features associated with a more differentiated, mature tissue state, while later first pregnancies were associated with profiles suggestive of incomplete stromal maturation. This mirrors the well-documented protective effect of early pregnancy, which is thought to drive the breast epithelium and its supporting tissue through a final differentiation program that reduces susceptibility to malignant transformation.

Breastfeeding also left its signature. Women with a history of lactation showed distinct stromal expression patterns compared with those who had never breastfed, a finding that aligns with epidemiological evidence that cumulative breastfeeding duration lowers breast cancer risk. The involution process that follows pregnancy and lactation—during which milk-producing structures are pruned back and the tissue remodels—involves waves of matrix breakdown and repair. The new data suggest that the stroma participates in this remodeling in ways that vary with lactation history and that these variations persist in tissue sampled years later, during routine clinical biopsies.

Number of births added further nuance. Multiparity, which epidemiological studies associate with a transient increase in risk shortly after pregnancy followed by long-term protection, was reflected in stromal marker expression patterns that differed from those of women with fewer births. The authors interpret these patterns as evidence that the stroma undergoes cumulative, history-dependent remodeling with each reproductive cycle. Rather than resetting completely after each pregnancy, the breast’s connective tissue framework appears to accumulate changes that integrate the number, timing, and character of reproductive events into a durable tissue phenotype.

The technical implications of the study extend beyond reproductive epidemiology. If stromal markers in benign biopsies encode risk-relevant biology, they could eventually serve as tissue-based biomarkers that sharpen risk assessment beyond what clinical and family history alone can provide. Current models of breast cancer risk—used to determine screening intensity and prevention strategies—rely heavily on demographic factors, reproductive history, mammographic density, and genetic variants. Incorporating quantitative stromal features from benign biopsies, which are already obtained and archived in routine clinical practice, could add a layer of biological information that is directly grounded in the microenvironment where cancers arise. The researchers caution that their findings establish associations, not causal mechanisms, and that validation in independent cohorts will be essential before any clinical application.

The study also speaks to a broader conceptual shift in cancer biology: the recognition that cancer risk is inscribed not only in the genome of epithelial cells but in the state of the tissue as a whole. The stroma of the breast changes dramatically across the reproductive lifespan—at puberty, with each menstrual cycle, during pregnancy and lactation, and at menopause—and each transition involves coordinated changes in fibroblast behavior, immune cell infiltration, matrix composition, and mechanical properties. The new findings suggest that these transitions are not fully reversible, and that the stroma retains a memory of reproductive events. Understanding how that memory is encoded—whether through epigenetic modifications in fibroblasts, persistent alterations in matrix cross-linking, or long-lived changes in stromal cell populations—is now a central question for follow-up research.

For the millions of women who undergo benign breast biopsies each year, the study offers a glimpse of a future in which the tissue removed during a routine procedure yields far more information than a simple benign diagnosis. By reading the stromal record of reproductive history alongside conventional pathological features, clinicians may one day better distinguish which benign lesions carry meaningful future risk. In the nearer term, the work provides a mechanistic bridge between decades of epidemiological observations about pregnancy, breastfeeding, and breast cancer, and the microscopic biology of the tissue microenvironment—demonstrating that the protective and risk-modifying effects of reproduction are, quite literally, woven into the fabric of the breast.

Subject of Research: Association between reproductive factors and stromal marker expression in benign breast biopsy samples

Article Title: Reproductive factors and the expression of stromal markers in benign breast biopsy samples

Article References: Ratcliffe, M., Heng, Y. J., Guzman-Arocho, Y. D., Rosner, B., Tamimi, R. M., & Yaghjyan, L. (2026). Reproductive factors and the expression of stromal markers in benign breast biopsy samples. British Journal of Cancer. https://doi.org/10.1038/s41416-026-03615-7

Image Credits: AI Generated

DOI: 10.1038/s41416-026-03615-7

Keywords: breast stroma, benign breast biopsy, reproductive factors, parity, breastfeeding, stromal markers, breast cancer risk, extracellular matrix, myofibroblasts, tissue microenvironment, age at first pregnancy, tissue remodeling

The answer, according to the new work, centers on monocytes, a population of white blood cells that circulates in the bloodstream and is best known as an emergency responder dispatched to sites of infection or injury. The research reveals that in the uterus, monocytes play a far more nuanced role than simply arriving to fight threats. They act as a continuous supply line, replenishing distinct subsets of uterine macrophages, the tissue-resident immune cells that orchestrate tissue remodeling, clear cellular debris and calibrate inflammatory responses throughout the reproductive cycle.

Macrophages are not a uniform population. In tissues across the body, they exist as specialized subsets, each tuned to particular functions. Some are heavily phagocytic, engulfing dead cells and remodelled extracellular matrix. Others are regulatory, producing signals that suppress damaging immune reactions and promote tissue tolerance. In the uterus, this specialization is especially pronounced, because the organ must alternately support inflammatory processes, such as the tissue breakdown that accompanies menstruation or the onset of labor, and anti-inflammatory states, such as the immune tolerance required during pregnancy.

One of the central discoveries of the study is that these uterine macrophage subsets are not self-sustaining. Unlike macrophages in some other tissues, which can persist for long periods by dividing locally, many uterine macrophage populations depend on continual replenishment from blood-borne monocytes. As the reproductive cycle progresses and the uterine landscape shifts from proliferative to secretory to menstrual phases, monocytes are recruited into the tissue and differentiate into the specific macrophage subsets required at each stage. This means the composition of the uterine immune system is actively rebuilt across every cycle rather than being fixed at steady state.

That arrangement is elegant in its responsiveness, but it also creates vulnerability. Because the system depends on a constant influx and correct differentiation of monocytes, any disruption to monocyte recruitment, survival or maturation can ripple outward, altering the balance of macrophage subsets and, with it, the integrity of the tissue environment. The researchers found evidence that such disruptions occur in reproductive disease, where the normal homeostatic loop between monocytes and macrophages breaks down, contributing to maladaptive inflammation and impaired tissue repair.

The concept of dual roles is key to interpreting these findings. On one hand, monocytes serve as builders and maintainers, supplying fresh macrophages that support regeneration and keep inflammation in check. On the other hand, monocytes are the raw material of inflammation itself. When recruited in excessive numbers or instructed inappropriately, they can differentiate into macrophage states that amplify inflammatory damage rather than resolve it. The same cellular pathway that sustains health can, when dysregulated, drive pathology. This duality helps explain why the uterus, with its repeated cycles of wounding and repair, is susceptible to inflammatory and remodeling disorders.

Technically, the study relied on a combination of modern single-cell approaches and lineage tracing, tools that allow researchers to follow individual cells and their descendants over time. By profiling the transcriptomes of uterine immune cells across different phases of the reproductive cycle, the team could map which macrophage subsets were present at each stage and infer their origins. Fate-mapping experiments then demonstrated directly that newly arriving monocytes, rather than long-lived resident cells dividing in place, gave rise to the replenished macrophage pools. Functional analyses connected these cellular dynamics to the tissue-level processes of remodeling and inflammation regulation.

The implications extend across a broad range of reproductive health conditions. Abnormal menstrual bleeding, endometriosis, adenomyosis, recurrent pregnancy loss, preterm birth and poor wound healing after childbirth have all been linked, to varying degrees, with altered macrophage activity in the uterus. The new framework provides a unifying explanation: if monocytes fail to replenish the right macrophage subsets at the right time, or if they replenish the wrong ones, the result can be tissue that remodels abnormally, inflammation that lingers when it should resolve, or repair that proceeds incompletely.

There is also a broader significance beyond reproductive biology. The finding that a major tissue macrophage compartment depends on continuous monocyte supply adds to a growing appreciation that tissue-resident macrophages in many organs occupy a spectrum, with some established before birth and self-maintained, and others continually renewed from blood. Where a given tissue sits on that spectrum likely shapes its disease susceptibility, its regenerative capacity and its response to therapy. The uterus, with its naturally recurring cycles of breakdown and rebuilding, offers an unusually accessible window into these dynamics.

For clinicians and drug developers, the work suggests potential avenues for intervention. If reproductive diseases arise from imbalances in the monocyte-to-macrophage pipeline, then strategies that modulate monocyte recruitment, guide their differentiation toward restorative macrophage states, or correct the signals that misdirect them could offer new treatments. Such approaches remain distant, and the researchers caution that the mechanisms linking monocyte-derived macrophages to specific disease processes still require detailed elaboration. But the study provides a clear cellular target and a conceptual map for future investigation into conditions that affect millions of people worldwide.

Subject of Research: The roles of uterine monocytes in replenishing uterine macrophages and maintaining tissue homeostasis across reproductive cycles in health and disease.

Article Title: The dual roles of uterine monocytes in regulation of tissue homeostasis throughout reproductive cycles in health and disease

Article References: Shahzad, A., Moran, O., Alebrahim, Y., Colombo, S., Lacerda Mariano, L., Shorthouse, O., Morgan, H., Bhatt, D., Scott, N., Hunter, F. K., Laverty, C., Ruane, P., Graham, G., Paterson, I., Kaur, N., Amin, Z., Lokman, M., Lin, I.-H., Murtuza-Baker, S., … Mann, E. R. (2026). The dual roles of uterine monocytes in regulation of tissue homeostasis throughout reproductive cycles in health and disease. Nature Immunology. https://doi.org/10.1038/s41590-026-02651-y

Image Credits: AI Generated

DOI: 10.1038/s41590-026-02651-y

Keywords: uterine monocytes, macrophages, tissue homeostasis, reproductive cycle, endometrium, inflammation, tissue remodeling, immunology, monocyte differentiation, reproductive disease, immune cells, uterus

The research, led by a team working at the interface of mechanobiology and skin biology, addresses a long-standing puzzle in tissue physiology. Skin must maintain structural integrity while simultaneously accommodating growth, wound repair, and chronic mechanical stress such as repeated friction or tension. How a tissue senses these forces and translates them into molecular remodeling programs has been studied extensively at the level of individual mechanosensitive channels and cytoskeletal adapters. Far less is understood about which specialized cell subpopulations act as the conductors of this whole-tissue response.

Fibroblasts, the connective tissue workhorses of the dermis, have long been treated as a relatively uniform population of cells that deposit collagen and other extracellular matrix components. Over the past decade, single-cell technologies have shattered that view, revealing that fibroblasts exist in a spectrum of functionally distinct states, each occupying specific anatomical niches and performing specialized duties. Among the markers that have drawn intense interest is LGR5, a receptor best characterized as a Wnt target gene and a hallmark of adult stem cells in the intestine, hair follicle, and several other organs. Its appearance on a subset of dermal fibroblasts hinted that these cells might occupy a privileged regulatory position within skin.

The new findings place those LGR5-positive fibroblasts at the center of what the authors describe as skin mechanoadaptation, the process by which the tissue adjusts its architecture and mechanical properties in response to physical forces. According to the study, when skin is subjected to mechanical loading, these cells do not merely respond passively. Instead, they act as orchestrators, integrating mechanical cues and broadcasting instructions to surrounding cells through inflammatory and remodeling pathways, with JAK1 serving as a critical signaling node in that communication.

JAK1, or Janus kinase 1, is a cytoplasmic tyrosine kinase that relays signals from a family of cytokine receptors into the cell interior, most famously activating the STAT transcription factors that drive genes involved in immunity, cell growth, and tissue repair. Drugs targeting the JAK family have transformed the treatment of inflammatory diseases and certain cancers, making JAK1 one of the most pharmacologically scrutinized kinases in modern medicine. The revelation that JAK1 functions as a mechanotransductive regulator within a specialized fibroblast subset adds an entirely new dimension to its biological portfolio, and suggests that mechanical stress and inflammatory signaling in skin are more deeply intertwined than previously appreciated.

The implications extend well beyond basic cell biology. Excessive or aberrant mechanical stress is implicated in a range of cutaneous pathologies, from hypertrophic scarring and fibrosis to pressure ulcers and the progressive stiffening of aged skin. Conversely, insufficient mechanoadaptation can compromise wound closure and tissue resilience. If LGR5-positive fibroblasts genuinely coordinate the tissue-wide response to force through JAK1 signaling, then therapeutic strategies aimed at this specific cellular niche could, in principle, recalibrate how skin responds to stress, promoting healthy remodeling while dampening pathological fibrosis.

To reach these conclusions, the research team combined state-of-the-art lineage tracing with mechanical perturbation of skin tissue. Genetic fate-mapping approaches, in which cells expressing LGR5 and their descendants are permanently labeled, allowed the investigators to follow the behavior of this fibroblast subset under basal conditions and in response to mechanical challenge. Complementing the lineage studies, transcriptomic profiling revealed the molecular identity of the mechanoadaptive program, pinpointing JAK1-dependent signaling as a central feature of how these cells translate physical input into changes in gene expression and, ultimately, tissue architecture.

When the investigators disrupted JAK1 function in the context of mechanical loading, the coordinated adaptive response faltered, supporting the model that LGR5-positive fibroblasts require this kinase to fulfill their regulatory role. The finding reframes mechanotransduction not as a cell-autonomous affair confined to force-sensing proteins at the membrane, but as an intercellular program in which a small population of specialized stromal cells interprets mechanical context and modulates the behavior of the tissue as a collective. In this view, fibroblasts act less like passive scaffolding cells and more like mechanical stethoscopes and loudspeakers rolled into one, listening to the physical state of the skin and broadcasting chemical instructions accordingly.

For the broader field of mechanobiology, the study contributes to a growing recognition that stromal cells are active participants in how organs sense and respond to their physical environment. Similar sentinel populations have been described in other tissues, where specialized fibroblasts guide immune responses, organize repair zones after injury, and maintain niche architecture. The identification of an LGR5-marked, JAK1-modulating subset in skin strengthens the argument that tissue-level mechanoadaptation depends on a division of labor among fibroblast states, and that understanding this division of labor is essential for regenerative medicine.

Translational questions now loom large. Because JAK inhibitors are already in widespread clinical use, the findings raise the possibility that existing drugs, or more selective derivatives, could be repurposed to modulate skin mechanoadaptation in contexts ranging from scar prevention to anti-fibrotic therapy. At the same time, the study serves as a caution: wholesale blockade of JAK signaling in skin could interfere with beneficial adaptive remodeling, and the challenge ahead lies in achieving the right specificity, both at the level of the kinase and at the level of the cell type. As researchers work toward that precision, the humble dermal fibroblast, once dismissed as connective tissue filler, has firmly claimed its place as a master regulator of how skin meets the mechanical world.

The choice of LGR5 as a marker reflects a broader shift in how biologists identify functionally important cell types. Because LGR5 marks actively cycling stem cells in rapidly renewing epithelia, its expression in the dermis initially suggested that these fibroblasts might retain an unusual developmental plasticity. Fate-mapping studies in other organs have shown that LGR5-positive populations can generate diverse progeny, and the present work extends that logic to the stromal compartment, where a marked subset appears to exert influence less through self-renewal than through signaling authority over its neighbors.

The dermal microenvironment in which these cells reside is itself worth considering. The dermis is organized into papillary and reticular layers with distinct collagen densities, vascular supplies, and resident cell compositions, and fibroblasts occupying these layers differ in gene expression and in the mechanical properties of the matrix they produce. Mechanical forces impinging on the skin surface are transmitted through this layered architecture in complex ways, so a subset positioned at a particular depth or niche may be uniquely situated to sense deformation and relay that information to immune cells, endothelial cells, and epithelial stem cells above.

The connection between mechanical loading and cytokine signaling illuminated here also fits with accumulating evidence that physical forces can modulate inflammatory pathways independently of infection or tissue damage. Stretch, compression, and fluid shear have all been shown to alter cytokine production in cultured cells, and the JAK-STAT pathway is a common downstream convergence point for such signals. Placing JAK1 within a mechanotransductive circuit in intact skin provides an in vivo anchor for observations that had largely been made in simplified culture systems, where the multicellular architecture of real tissue is absent.

From a clinical standpoint, the findings intersect with a persistent therapeutic dilemma in dermatology. Antifibrotic interventions aim to reduce excessive collagen deposition, yet collagen synthesis is also essential for normal wound healing, and blunt suppression of matrix production can impair closure and strength of repaired skin. A regulatory node that acts specifically during mechanical adaptation offers a potential middle path: modulating it might allow clinicians to distinguish pathological responses to chronic aberrant loading from the beneficial remodeling that follows injury or surgical repair.

The study also speaks to the biology of skin aging, in which the dermis loses elasticity and becomes progressively stiffer, in part through changes in fibroblast number, phenotype, and extracellular matrix turnover. Whether the LGR5-positive mechanoadaptive population declines, shifts state, or becomes functionally silenced with age is an obvious next question, and one that could connect mechanoadaptation to the well-documented observation that aged skin heals more slowly and scars differently than young skin.

Methodologically, the work illustrates the value of combining lineage tracing with controlled mechanical perturbation, an approach that is becoming more common as researchers recognize that static snapshots of gene expression cannot capture how cells respond dynamically to force. Transcriptomic profiling under defined loading conditions, paired with genetic disruption of candidate signaling mediators, provides a framework that other groups studying lung, gut, or cardiovascular mechanobiology may adapt, since stromal sentinel populations are increasingly suspected in those organs as well.

Important caveats remain before the model can be considered complete. Mouse studies with genetic fate mapping do not automatically translate to human skin, whose dermal architecture and fibroblast heterogeneity differ in notable ways, and the precise identity of the upstream mechanical sensor in these cells has yet to be defined. Whether JAK1 modulation acts directly on mechanosensitive transcription or indirectly through cytokines released by neighboring cells will require careful dissection. Nonetheless, the demonstration that a defined fibroblast subset can govern tissue-wide mechanical adaptation marks a substantive step toward a cell-type-resolved understanding of how skin endures the physical demands of daily life.

Subject of Research: The role of LGR5-positive fibroblasts in coordinating skin mechanoadaptation via JAK1 signaling

Article Title: LGR5-positive fibroblasts orchestrate skin mechanoadaptation through JAK1 modulation

Article References: Fu, Q., Cheng, X., Chen, N., Sun, Y., Xu, L., Cheng, Y., Wang, C., Li, Y., Yu, T., Yan, Y., Zhang, W., Bu, Y., Lei, L., Chen, Y., Li, Z., Zhu, P., Wang, C., Zhang, L., Liu, C., & Li, Q. (2026). LGR5-positive fibroblasts orchestrate skin mechanoadaptation through JAK1 modulation. Nature Communications. https://doi.org/10.1038/s41467-026-77113-y

Image Credits: AI Generated

DOI: 10.1038/s41467-026-77113-y

Keywords: LGR5, fibroblasts, skin, mechanoadaptation, JAK1, mechanotransduction, Nature Communications, dermis, tissue remodeling, JAK inhibitors, single-cell analysis, skin biology