The meninges consist of three layers—the pia mater hugging the brain surface, the arachnoid mater above it, and the dura mater outermost. Together they anchor the brain to the skull, carry its blood supply, house immune defences, and provide the channels through which cerebrospinal fluid flows. Despite their clinical importance, no one had ever produced a single-cell atlas of the human meninges during development. That gap mattered, because tumours are known to hijack developmental programs, and identifying a tumour’s cell of origin often requires comparing it against the normal cell types present during organ formation.

To close that gap, the researchers collected meningeal tissue from 16 samples spanning postconceptional weeks 5 through 13, obtained from elective abortions with informed consent under approved ethical protocols. Using droplet-based single-cell RNA sequencing, they profiled 156,726 high-quality cells, which they organised into 245 clusters annotated across four hierarchical levels: 115 cell types, 105 subclasses, 45 classes and 8 superclasses. Fibroblasts marked by the transcription factor FOXC1 made up roughly half the dataset, alongside PECAM1-positive endothelial cells, ABCC9-positive perivascular cells, PTPRC-positive immune cells and even anucleated erythropoietic cells. Interacting neural, neural crest and choroid plexus epithelial cells were also captured, giving the atlas an unusually complete view of the brain’s outer environment.

Crucially, the team paired the sequencing with spatial transcriptomics using the Xenium platform, cryosectioning entire embryonic heads at weeks 6 and 9.5 so that the meninges remained anatomically intact. A custom probe panel targeting 389 genes, chosen from the sequencing data, allowed them to locate each cell type in situ. At week 6 they identified the primary meninx, the earliest meningeal structure described in the literature, a thin fibroblast sheet wrapping the entire brain together with FOXQ1-positive endothelial cells. By week 9.5, the spatial data revealed a remarkably complete stack of tissue layers, from the ventricular zone of the developing cortex up through Cajal–Retzius cells, meningeal fibroblasts, the future skull, periosteum and skin.

One of the atlas’s most consequential findings concerns how the three meningeal layers form. Rather than branching off from distinct precursor lineages the way blood cells do in haematopoiesis, the pia, arachnoid and dura emerged as a continuum of cell states. Layer-specific markers—LAMC3 for pia, SLC22A6 for arachnoid and COL8A1 for dura—showed smooth gene expression gradients at every age examined, and maturation scores built from adult layer-enriched genes revealed that all three layers mature concurrently, their adult gene programs already active in the first trimester and steadily increasing through week 13. Cycling cells were present in every layer, further supporting a model of parallel, gradual refinement rather than branched lineage commitment.

Within the dura, the spatial data exposed an unexpected subdivision. Beyond the thick outer dura, which expressed MSX2 and blended into osteogenic skull and periosteal tissues, the researchers found a distinct inner dura: a single sheet of cells apposed directly onto the arachnoid, marked by SLC47A1 and, surprisingly, the epithelial marker CDH1. This inner layer expressed a full complement of tight-junction genes—Occludin, several Claudins, junctional adhesion molecules and their intracellular scaffolds—plus adherens junction components and even tricellular junction proteins. In other words, the inner dura looks like a second barrier layer, histologically resembling arachnoid barrier cells rather than ordinary dura. Because the same CDH1-positive inner dura appears in adult human and mouse meninges, the team proposes that the complete meningeal barrier may be built from two cell sheets—the arachnoid barrier and the inner dura—and suggests renaming it the arachnoid–dura barrier.

The atlas also delivered surprises well beyond the dura. The fetal meninges harboured 19 immune cell types as early as week 5, including macrophages tiled sparsely across the primary meninx, microglia confined to the brain side of the leptomeningeal boundary, and—remarkably—B-lineage cells. CD34-positive, IL7R-positive, CD19-low early lymphoid progenitors appeared in the meninges at week 5, a full week earlier than such cells had been reported in fetal liver, and matured through pre-pro, pro, pre and immature B cell stages by weeks 8 to 13. This positions the meninges as an unexpected site of early human B cell differentiation. The vascular analysis was equally revealing: venous endothelial cells expressing the lymphatic transcription factor PROX1 suggested that subarachnoid lymphangiogenesis may begin in early fetal life, whereas in mice meningeal lymphatics develop only after birth.

The pivotal question, however, was what all this says about meningiomas. The team reanalysed published single-cell and bulk RNA sequencing data from human meningiomas and generated new Xenium spatial data from seven tumours, including one grade I and six grade III tumours. Using latent Dirichlet allocation topic modelling—a computational method that identifies co-expressed gene modules corresponding to cell identities—they defined 35 topics from the fetal fibroblast data, including topics for pia, arachnoid, inner dura, outer dura and a barrier topic shared between arachnoid and inner dura cells. When these topics were transferred to the tumour data, the result was unambiguous: pia and arachnoid topics were nearly absent, while inner dura, dura and barrier topics dominated. Tumour cells expressed CDH1 and SLC47A1 but showed no detectable SLC22A6, the arachnoid marker. The same pattern held in bulk RNA sequencing of 185 meningiomas across grades I to III, with dural topics dominating in merlin-intact, immune-enriched and hypermitotic methylation subtypes alike.

Genetic evidence pointed the same way. Because both tumour suppressors and oncogenes must normally be expressed in a cell before transformation can occur, the researchers compiled the 20 most frequently mutated genes in meningiomas from the COSMIC Cancer database and measured their collective expression across the fetal and adult meningeal cell types. The dural lineage—particularly committed dura precursors and inner dura cells—showed by far the highest expression of these putative cancer drivers, a result that persisted even after removing genes commonly mutated in glioblastoma, intestinal or pancreatic cancers. The authors are careful to frame this as a hypothesis rather than a settled fact: it remains possible that tumours arising from arachnoid barrier cells later convert to a dura-like state, and previous mouse models that generated meningiomas from PTGDS-expressing cells did not distinguish arachnoid barrier from inner dura, since PTGDS is expressed in both. Still, the convergence of spatial, single-cell, bulk and genetic lines of evidence makes dural cells a serious new candidate for the meningioma cell of origin.

The clinical implications could be substantial. Higher-grade atypical and anaplastic meningiomas currently have no effective drug therapies, a failure partly attributed to decades of uncertainty about what these tumours actually are. If meningiomas are, at a transcriptional level, dural tumours, then therapeutic strategies, animal models and drug screens designed around arachnoid biology may have been aiming at the wrong target. The atlas itself—freely available through public repositories including the European Genome-Phenome Archive and GitHub—now provides the reference framework the field has lacked, charting not only the fibroblast layers but the immune, vascular and choroid plexus cells that co-develop with them. Whether dura-lineage cells can truly give rise to meningiomas will require lineage-tracing and functional experiments, but this study has, for the first time, given the question a molecular foundation—and in doing so, it has reopened a debate that medicine thought it had closed more than 150 years ago.

Subject of Research: Single-cell and spatial transcriptomic mapping of human fetal meninges development and its implications for the cellular origin of meningiomas

Article Title: Cell atlas of the developing human meninges reveals a dura-like nature of meningiomas

Article References: Vinsland, E., Marco Salas, S., Kapustová, I., Hu, L., Webb, S., Li, X., He, X., Nilsson, M., Haniffa, M., Barker, R. A., Persson, O., Raleigh, D. R., Sundström, E., Lönnerberg, P., & Linnarsson, S. (2026). Cell atlas of the developing human meninges reveals a dura-like nature of meningiomas. Nature Cell Biology. https://doi.org/10.1038/s41556-026-02074-9

Image Credits: AI Generated

DOI: 10.1038/s41556-026-02074-9

Keywords: meninges, meningioma, dura mater, arachnoid, single-cell RNA sequencing, spatial transcriptomics, fetal development, cell atlas, brain tumours, fibroblasts, tight junctions, cell of origin

The research team, based at the Eye Center of the Second Affiliated Hospital of Zhejiang University School of Medicine, analyzed anterior lens capsules from 554 patients undergoing cataract surgery between October 2022 and December 2024. The patients were divided into three clinically recognized groups using the Lens Opacities Classification System II: 185 with mild cataracts, 210 with severe cortical cataracts, and 159 with severe nuclear cataracts. Using single-nucleus RNA sequencing, the researchers profiled a staggering 230,838 lens epithelial cells, building one of the most comprehensive cellular atlases of the aging lens capsule assembled to date.

Lens epithelial cells are the only proliferative cells in the lens, and they are essential for maintaining its transparency. Sitting just beneath the anterior capsule, they continuously renew lens fibers and shield the organ from oxidative stress and external damage. When their function deteriorates with age, cataracts follow. But until now, scientists had lacked a detailed map of the distinct cell states within this microenvironment, and how those states shift as cataracts progress from mild clouding to severe opacification.

The atlas revealed seven functionally distinct subpopulations of lens epithelial cells, which the team named according to their dominant gene expression profiles: secretory, regulatory, protective, metabolic, homeostatic, fibrotic, and extracellular-matrix-regulatory cells. As disease advanced, the proportions of the protective, homeostatic, and fibrotic subpopulations steadily declined, while the extracellular-matrix-regulatory group expanded. This shifting balance suggests that specific cell states govern the transitions between mild and severe disease, and that preserving vulnerable subpopulations might one day slow or prevent progression.

The most striking discovery concerned the secretory subpopulation, designated Cluster 0. Gene enrichment analyses showed that neurotrophic signaling pathways, particularly the SLIT-ROBO pathway, which normally guides axonal growth and neural progenitor proliferation, were active across the cataract groups. Immunofluorescence staining then confirmed the presence of beta-III tubulin-positive, axon-like structures penetrating the capsular periphery of cataract patients. No such structures were detected in the transparent lens capsules of healthy organ donors. In severe nuclear cataracts, the density of these axon-like projections was roughly eight to sixteen times higher than in the mild and severe cortical groups, respectively.

To trace the origin of these signals, the team integrated their lens data with single-nucleus sequencing data from human sympathetic ganglia. The analysis identified a specific neuronal subcluster, Sympathetic_neurons2, as the most interactive neural population, and pinpointed a molecular axis at the heart of the communication: Cluster 0 cells express high levels of the neurotrophic factor NRG1, which pairs with the ERBB3 receptor on sympathetic neurons. Immunofluorescence confirmed that both NRG1 and ERBB3 were dramatically elevated in severe nuclear cataract capsules compared with normal tissue, with NRG1 expression increasing several hundredfold.

Within Cluster 0 itself, further subclustering revealed three cell states: S100A4-positive, SYN3-positive, and MT-CO1-positive lens epithelial cells. As cataracts progressed, the SYN3-positive population, associated with neurotrophic signaling, expanded, while the MT-CO1-positive population, tied to mitochondrial energy production, shrank. This pattern echoes earlier findings that the mitochondrial protein MT-CO1 is upregulated early in cataract development to sustain ATP production but collapses in advanced opacification, and that Synapsin III expression rises in aged lenses, potentially reflecting age-related stress responses.

The study also documented a breakdown in the mechanisms that normally restrain nerve growth. SEMA3 signaling, which repels axons and prevents them from invading inappropriate tissue regions, shifted from coordinated expression across multiple cell subpopulations in mild cataracts to dominance by single clusters in severe disease. The researchers propose that this loss of inhibitory control, combined with aging-driven activation of NRG signaling, permits aberrant axonal proliferation into the capsule. Meanwhile, distinct metabolic signatures separated the two severe subtypes: cortical cataracts were enriched for calcium transport pathways, a known driver of lens protein degradation, while nuclear cataracts showed activation of ferroptosis pathways, the iron-dependent cell death process increasingly implicated in lens clouding.

The clinical implications are tantalizing. Because the NRG1-ERBB3 axis appears to be a central driver of the neural ingrowth associated with cataract progression, the authors suggest that targeted therapies, such as NRG1 antibodies, could eventually modulate these neurotrophic pathways. Prior work has shown that ERBB-family signaling participates in lens fibrosis and epithelial-mesenchymal transition after cataract surgery, and that NRG1 signaling can suppress stress-induced cellular senescence in vascular tissue, lending plausibility to the idea that manipulating this axis could influence lens aging more broadly. Still, the researchers caution that their study has limits: single-nucleus sequencing requires dissociating tissue, severing the spatial relationships between cells, and the exact origin of the axon-like structures remains unresolved.

The team plans to address these gaps with spatial transcriptomics, which preserves tissue architecture while mapping gene expression, and with functional validation of axonal growth in organoid-based models. For now, the study reframes age-related cataracts as a disease of cellular heterogeneity and aberrant neuro-lens communication rather than a uniform degenerative process. With the global population aged 60 and over projected to grow by 1.4 billion by 2030, and cataract prevalence exceeding 92 percent in people over 80, understanding the molecular choreography of lens aging has never mattered more. If the neural invasion of the aging lens can be intercepted, the first genuine preventive treatment for the world’s leading cause of blindness may become a realistic goal.

Subject of Research: Single-nucleus sequencing of human age-related cataract lens capsules identifying neural ingrowth and cell subpopulations in lens aging

Article Title: Deconstruction of Human Age‐Related Cataract Capsules Defines Aging

Article References: Tang, Q., Tong, Z., Fan, C., Chen, S., Guo, J., Hu, J., Yao, K., Yin, Z., Chen, X., & Yu, Y. (2026). Deconstruction of Human Age‐Related Cataract Capsules Defines Aging. Advanced Science, 13(55), Article e76532. https://doi.org/10.1002/advs.76532

Image Credits: AI Generated

DOI: 10.1002/advs.76532

Keywords: age-related cataract, lens epithelial cells, single-nucleus RNA sequencing, NRG1-ERBB3 signaling, neural ingrowth, lens capsule, SLIT-ROBO pathway, ferroptosis, calcium signaling, mitochondrial dysfunction, cell atlas, sympathetic neurons

Single-cell RNA sequencing, or scRNA-seq, does something deceptively simple: instead of measuring the collective gene activity of an entire tissue, it profiles the transcriptome of individual cells. The transcriptome, the complete set of RNA molecules in a cell, acts as the bridge between the static genome and dynamic biological function. Bulk transcriptomics blurs this picture, masking the heterogeneity of the many cell types that make up even a small organ such as a mosquito midgut. By deconstructing tissues into their constituent cells, scRNA-seq allows researchers to discover rare cell populations, reconstruct developmental trajectories and map communication networks between cells. The technology has already driven breakthroughs in oncology, neuroscience and virology, and the review’s authors, led by Li-Bo Liu and Jia-Hong Wu of Guizhou Medical University, contend that mosquitoes are its next great frontier.

The technical pipeline is demanding at every step. Researchers must dissect tissues or collect hemolymph, isolate single cells or nuclei, capture them, prepare sequencing libraries and run high-throughput sequencing before any computational analysis begins. Each choice carries biological consequences. Enzymatic dissociation can stress cells and induce artificial transcriptional responses, and fragile or large cell types may be selectively lost. For tissues that resist dissociation, such as the brain or fat body, single-nucleus RNA sequencing offers an alternative that preserves cell-type proportions, though at the cost of losing cytoplasmic transcripts. The incorporation of unique molecular identifiers allows digital counting of original transcripts and mitigates amplification bias, while the choice between plate-based methods such as Smart-seq2, which deliver near-complete transcript coverage of relatively few cells, and droplet-based systems such as 10x Genomics Chromium, which profile tens of thousands of cells at shallower depth, fundamentally shapes what can be observed.

These trade-offs are not abstract. In studies of the malaria mosquito Anopheles gambiae, the high throughput of 10x Chromium succeeded in capturing megacytes, a rare hemocyte subpopulation making up only about 0.5 percent of immune cells, whereas Smart-seq2’s superior sensitivity identified phagocytic granulocytes that the droplet platform missed. Both findings were validated by in situ hybridization, confirming that the discrepancies stemmed from technical characteristics rather than false positives. The review’s authors emphasize that such variation demands rigorous reporting standards, including adherence to emerging minimum-information guidelines for single-cell experiments, explicit documentation of platforms and computational parameters, and independent validation of novel cell types before they are accepted as biological reality rather than computational artifacts.

What has the technology actually revealed? Perhaps the most striking lesson is that classical cell classifications were far too coarse. Mosquito hemocytes, the insect immune cells, were traditionally divided into granulocytes, oenocytoids and prohemocytes. Single-cell profiling has exploded this scheme into a multilevel system, showing that granulocytes comprise conventional, proliferative, antimicrobial and phagocytic subtypes, alongside megacytes that appear to coordinate immune responses mediated by hemocyte differentiation factor. Intriguingly, megacytes were not detected in Aedes aegypti, suggesting genuinely distinct immune lineages among vector species rather than a technical artifact, and challenging the assumption of a universal insect immune cell blueprint. The midgut epithelium has undergone a similar refinement: enterocytes once treated as a uniform class now resolve into five subtypes enriched for distinct digestive enzymes or immune factors, while enteroendocrine cells split into three subtypes specializing in different neuropeptide signals.

ScRNA-seq has also uncovered cell populations that fit no existing category. In the fat body of blood-fed Aedes aegypti, researchers identified fat-body-yolk cells, which coexpress markers of metabolic fat body tissue, ovarian reproductive tissue, stem cell genes and even eggshell formation genes. Their persistence after a blood meal, even when no oviposition sites are available, hints at a poised state dedicated to maintaining reproductive readiness, a possible adaptation to unpredictable breeding opportunities. The authors caution, however, that transcriptional identity does not equal validated function; the hypothesized roles of these cells in lipid transport, resource reallocation and defense remain compelling but untested. Cell atlases have now been extended to salivary glands, testes and the nervous system, laying groundwork for a comprehensive reference that could inform next-generation insecticides, gene-drive strategies and transmission-blocking interventions.

The technology’s power to dissect dynamic physiology is vividly illustrated by the response to a blood meal, the event that makes mosquitoes dangerous. Within one day of feeding, three nascent enterocyte clusters surged from 0.4 percent to 52.2 percent of midgut cells, an expansion too rapid for new cell generation and one that points to transdifferentiation of existing cells, though the origin remains unresolved. In the fat body, trophocyte proportions shifted between two and seven days post-feeding, with upregulation of trehalose synthesis genes and immune regulators coupling metabolic reprogramming to immune activation. Hemocyte numbers doubled by day seven, and even the brain participated: single-nucleus sequencing revealed dramatic transcriptional changes in glial cells within three hours of feeding, including upregulation of steroid hormone receptors and circadian clock genes, implicating glia as regulators of the post-blood-meal behavioral switch.

Sexual dimorphism, too, has acquired a cellular basis. Female Aedes aegypti brains are enriched for specific Kenyon cells, dopaminergic neurons and projection neurons, while male brains contain higher proportions of particular glial cells and other neuronal classes. Sex-biased gene expression follows, with males showing higher expression of the sex determination factor Nix and females expressing dipeptidyl peptidases at elevated levels. Notably, the sex determination gene doublesex is more highly expressed in glial cells than in neurons, suggesting an underappreciated role for glia in establishing sexual identity. In sensory organs, male-specific epithelial-like cells in antennae and female-specific neurons in the proboscis provide cellular correlates for sex-specific behaviors such as host-seeking. Single-nucleus data have likewise challenged the one neuron–one receptor dogma of sensory coding, revealing frequent coexpression of odorant and ionotropic receptors, and coexpression of taste and temperature sensors in gustatory neurons, expanding the theoretical coding capacity of the mosquito nervous system.

The most consequential applications may lie in host–pathogen interactions. Conventional scRNA-seq pipelines discard non-host reads as contamination, but adapted protocols, notably 5′ capture methods compatible with microfluidic platforms, can capture viral RNAs that lack polyadenylated tails. Using such approaches, researchers found that Zika virus preferentially targets enteroendocrine cells and enterocytes in the Aedes aegypti midgut, while West Nile virus reaches its highest loads in enteroendocrine cells of Culex tarsalis, hinting at a conserved flaviviral susceptibility tied to these cells’ signaling and secretory functions. In Anopheles gambiae, dual host–parasite sequencing showed that Plasmodium ookinetes preferentially interact with midgut progenitor cells during epithelial traversal, an interaction conserved across Anopheles species and parasite isolates. Immune responses are equally illuminating: enterocytes infected with Zika express antimicrobial peptides, whereas West Nile virus infection in Culex tarsalis produced no broad tissue-level immune activation, a finding that challenges the midgut’s reputation as a key site of innate immune defense and may partly explain that species’ vector competence.

These discoveries are already generating testable intervention targets. The enrichment of apolipophorin III in Zika-infected enteroendocrine cells led to RNA interference experiments confirming that this lipid transport protein supports viral replication, marking it as a candidate target. Similarly, single-cell analysis identified the LL3 gene as highly expressed in megacytes and essential for the hemocyte differentiation factor-mediated anti-Plasmodium response, establishing a rare cell type as a critical regulatory node in malaria vector immunity. The review’s authors are candid about remaining obstacles: cell annotation still leans heavily on Drosophila orthology, atlases remain incomplete for organs such as ovaries and compound eyes, and most findings await functional validation. The path forward, they argue, lies in integrating spatial transcriptomics, single-cell multiomics and perturbation-based experiments to build predictive models of mosquito–pathogen interactions. If that integration succeeds, single-cell insights accumulated over the past several years could mature from a discovery engine into the foundation of a new generation of targeted vector control strategies.

Subject of Research: Application of single-cell RNA sequencing to mosquito biology and mosquito–pathogen interactions

Article Title: Single-cell RNA sequencing unravels mosquito biology and host–pathogen interactions

Article References: Liu, L.-B., Ye, H.-B., Tian, Z.-H., Zeng, X.-H., & Wu, J.-H. (2026). Single-cell RNA sequencing unravels mosquito biology and host–pathogen interactions. Parasites & Vectors, 19(1), Article 426. https://doi.org/10.1186/s13071-026-07460-8

Image Credits: AI Generated

DOI: 10.1186/s13071-026-07460-8

Keywords: single-cell RNA sequencing, mosquito, vector biology, host–pathogen interactions, cell atlas, Zika virus, West Nile virus, Plasmodium, malaria, dengue, vector control, transcriptomics

The research, conducted by an international team of investigators, presents a comprehensive comparative resource for adult human and mouse adrenal glands built on two complementary technologies: single-cell transcriptomics, which profiles the gene activity of thousands of individual cells, and spatial transcriptomics, which maps where those gene-expression programs reside within the intact architecture of the organ. By combining these approaches, the authors have produced what is effectively a high-resolution atlas of the adrenal gland in two species, capturing not only which cell types exist but also how their molecular identities and locations differ between human and mouse.

The significance of this resource lies in what it corrects. The adrenal cortex, the outer layer of the gland, is organized into zones that produce different classes of steroid hormones. In the classical textbook model, mineralocorticoids such as aldosterone are produced in the outermost zone, glucocorticoids such as cortisol in the middle zone, and androgen precursors in the innermost zone. This zonal model was largely established through work in rodents. The new single-cell and spatial data confirm that while broad zonal logic exists in both species, the underlying cellular states, the repertoire of expressed enzymes and the dynamics of cell differentiation diverge substantially between human and mouse, meaning that findings in mice cannot be assumed to apply directly to human adrenal physiology.

One of the study’s central findings concerns steroidogenic states. Steroid-producing cells do not represent a single, fixed identity; instead, they occupy a spectrum of molecular states defined by which steroidogenic enzymes they express, at what levels, and in what combinations. The comparative analysis shows that these states are shaped by species-specific programs. Human adrenal cells display enzymatic configurations and regulatory signatures that differ from their mouse counterparts in ways that affect how hormone synthesis is partitioned across the gland. For researchers studying disorders such as congenital adrenal hyperplasia, adrenal insufficiency, Cushing’s syndrome and primary aldosteronism, this is a critical caveat: therapeutic strategies validated in mouse models may engage cellular programs that human adrenal tissue either lacks or deploys differently.

The second major theme of the study is tissue turnover. The adrenal cortex is one of the most dynamic organs in the body, with its steroid-producing cells continuously replaced throughout life. The prevailing model, again derived largely from rodent studies, holds that a cap of progenitor cells near the outer surface of the gland continuously generates new steroidogenic cells that migrate inward, mature, perform their hormonal duties and eventually die, a conveyor-belt-like process of renewal. The new human data reveal that this turnover process, while conceptually conserved, proceeds with species-specific characteristics. The cellular sources of renewal, the differentiation trajectories and the pace of cell replacement differ between human and mouse, underscoring that the mouse conveyor-belt model is an approximation rather than a faithful replica of human adrenal maintenance.

Technically, the study’s strength comes from its dual-method design. Single-cell RNA sequencing excels at resolving cellular heterogeneity, distinguishing rare cell populations and reconstructing differentiation trajectories from the gene-expression fingerprints of individual cells. But dissociating an organ into single cells destroys spatial context, which is essential in an organ as architecturally organized as the adrenal gland. Spatial transcriptomics restores that context by measuring gene activity in intact tissue sections, allowing the researchers to verify that the cell states identified in the single-cell data occupy coherent anatomical positions. By applying both methods in parallel to human and mouse adrenal glands, the team could cross-validate cell-type assignments and map species differences with confidence, producing a resource designed to serve as a reference standard for the field.

The comparative framing also carries implications for regenerative medicine and drug development. Efforts to grow functional adrenal tissue in the laboratory, whether from stem cells or organoid cultures, depend on knowing which molecular programs must be activated to generate authentic steroid-producing cells. If those programs are species-specific, protocols optimized against mouse reference data may steer human cells toward the wrong developmental endpoints. Conversely, a human adrenal atlas provides a benchmark against which laboratory-grown adrenal cells can be quality-controlled, accelerating the path toward cell-based therapies for patients whose adrenal glands no longer function.

The resource is also expected to inform cancer research. Adrenocortical carcinoma is a rare but aggressive malignancy with limited treatment options, and its cellular origins remain incompletely understood. A detailed map of normal adrenal cell states in humans, including the progenitor populations and differentiation intermediates that tumors may hijack, offers researchers a framework for identifying which programs are reactivated in cancer and for designing therapies that target tumor-specific vulnerabilities while sparing normal steroid production.

Beyond disease, the study speaks to a broader lesson in modern biology: organ-level conclusions drawn from one species do not automatically transfer to another, even for organs as structurally similar as human and mouse adrenals. Evolution has conserved the gland’s essential function, the synthesis of life-sustaining steroids, but has implemented that function through partly divergent cellular and molecular means. As single-cell atlases accumulate across tissues and species, this theme recurs, and the adrenal gland now stands as a particularly clear example because its physiology is so directly tied to clinically essential hormones.

The authors have made their comparative dataset available as a community resource, allowing endocrinologists, developmental biologists and computational scientists to query cell-type markers, explore spatial gene-expression patterns and test their own hypotheses against the data. In an era when mouse models remain indispensable but increasingly scrutinized, resources of this kind provide the translational bridge that the field needs: a way to know precisely where the mouse is a faithful model of human biology, and where it is not. For the adrenal gland, at least, the answer is now written cell by cell, and it is more species-specific than anyone had fully appreciated.

Subject of Research: Comparative single-cell and spatial transcriptomic analysis of adult human and mouse adrenal glands

Article Title: Human and mouse adrenal glands are characterized by species-specific steroidogenic states and tissue turnover

Article References: Kastriti, M. E., Maksimov, D., Krupinova, J., Utkina, M., Beltsevich, D., Roslyakova, A., Glazova, O., Kaziakhmedova, S., Ryabova, A., Kuznetsova, A., Shcherbakova, A., Bondarenko, E., Antysheva, Z., Albert, E., Urusova, L., Lapshina, A., Chevais, A., Avsievich, E., Trofimov, V., … Adameyko, I. (2026). Human and mouse adrenal glands are characterized by species-specific steroidogenic states and tissue turnover. Nature Genetics, 58(9), 2270-2283. https://doi.org/10.1038/s41588-026-02737-1

Image Credits: AI Generated

DOI: 10.1038/s41588-026-02737-1

Keywords: adrenal gland, single-cell transcriptomics, spatial transcriptomics, steroidogenesis, tissue turnover, human-mouse comparison, adrenal cortex, hormone production, cell atlas, Nature Genetics, endocrinology, regenerative medicine