A central theme is the dynamic interplay among epithelial, stromal, immune, endocrine, and metabolic components of the mammary niche, which together regulate stem cell activity and tissue homeostasis. Epithelial and mesenchymal stem cell populations are described as playing distinct but complementary roles in mammary development, regeneration, and tissue maintenance, with their interactions within the tissue microenvironment shaping organ function.

Metabolic regulation emerges as a key mechanism, illustrated by the role of mechanistic target of rapamycin complex 1, or mTORC1, in mammary epithelial stem cell regulation. Evidence from the mammary gland indicates that intermittent inhibition of mTORC1 can increase stem cell activity, with potential implications for mammary development, lactational capacity, and persistency. The review is careful to note, however, that effects on whole-animal milk production remain to be established, marking this as an area where mechanistic findings have not yet been translated to production outcomes.

Mesenchymal stem cells receive particular attention, both as resident mammary stromal populations and as potential external mediators of epithelial–stromal communication. According to the review, these cells may integrate metabolic, endocrine, and inflammatory signals and contribute to tissue homeostasis and repair. Their therapeutic potential is discussed in the context of bovine mastitis, where mesenchymal stem cell-based approaches remain experimental. In that setting, the cells may act through paracrine signaling, immunomodulatory effects, and experimentally supported antimicrobial mechanisms, although the review frames these as investigational rather than established treatments.

The authors conclude that current evidence supports distinct but complementary roles for epithelial and mesenchymal stem cell populations in mammary development, regeneration, and tissue maintenance, while underscoring the limits of present knowledge. Defining these populations and mapping their interactions within the mammary niche, they argue, may inform stem cell-based approaches to mammary health and regeneration in humans and to health and production in farm animals. As a review, the work integrates existing findings rather than presenting new experimental data, and its translational outlook depends on future studies resolving how these cellular programs operate in vivo across species.

Subject of Research: Epithelial and mesenchymal stem cell biology in the mammary gland

Article Title: Epithelial and mesenchymal stem cell biology in the mammary gland: mechanisms, comparative insights, and translational perspectives

Article References: Barash, I. (2026). Epithelial and mesenchymal stem cell biology in the mammary gland: mechanisms, comparative insights, and translational perspectives. Frontiers in Cell and Developmental Biology, 14, Article 1982804. https://doi.org/10.3389/fcell.2026.1982804

Image Credits: AI Generated

DOI: 10.3389/fcell.2026.1982804

Keywords: mammary gland, stem cells, epithelial cells, mesenchymal stem cells, mTORC1, lactation, bovine mastitis, tissue regeneration, mammary niche, metabolic regulation, Epithelial, mesenchymal

Lead author Santanu Bose, a professor in WSU’s College of Veterinary Medicine, said the researchers first found evidence that the pathway was naturally activated during infection, but that the activation was not very robust. They identified the cellular factor that switches it on and then used a synthetic factor to amplify that activation. Adding recombinant ISG15 protein significantly increased cells’ resistance to infection. The resulting mechanism strengthens the cells’ own protective machinery rather than directly targeting viral components.

Technically, the study describes a non-canonical form of ISGylation mediated by integrin-FAK signaling and triggered by extracellular ISG15. ISG15 was already known to be induced internally during viral infection and had also been observed outside cells, but its extracellular function was unclear. The experiments indicate that external ISG15 can activate a previously unknown antiviral pathway, helping cells prepare for resistance before infection spreads through surrounding tissue. The approach therefore differs from an antiviral strategy that acts directly on viral proteins or other viral targets.

RSV was the principal virus used in the peer-reviewed experiments. It is a common respiratory virus that can cause severe illness in infants, older adults and people with weakened immune systems, but the reported results concern resistance in cultured epithelial cells rather than outcomes in an animal or human trial. Unpublished follow-up experiments from Bose’s laboratory, described in the WSU news release, also demonstrated antiviral activity against influenza A and parainfluenza viruses. The supplied material does not provide the methods, measurements or limitations of those unpublished results, so their scope cannot be independently evaluated from the peer-reviewed findings.

The host-directed mechanism has a potential advantage that remains to be tested broadly: mutations that alter viral targets and allow a treatment to stop working would not necessarily disrupt a strategy operating through the host cell’s own machinery. Bose said this could make the approach less vulnerable to viral mutation and potentially useful against a broad range of viruses, but the study did not demonstrate such breadth in people or in an animal model. The researchers are developing the method as a possible antiviral therapeutic, while WSU’s Innovation & Entrepreneurship team is working with them on patent protection and commercialization. That work includes an active option for a biotechnology company to explore further development.

The investigators also see possible relevance beyond infectious disease because the pathway stimulates cellular events that could be beneficial in cancer, neurological disorders and other conditions. They are exploring whether the same method of increasing pathway activation could be applied in non-infectious therapeutic settings. Those wider applications remain under investigation: the reported peer-reviewed study established increased antiviral resistance in cells, while the proposed use of recombinant ISG15 as a treatment and its possible benefits for other diseases have not been clinically established.

The project was led by graduate students Lindsay Grace Miller, who initiated the work, and Sudiksha Pandit, together with Fulbright Postdoctoral Scholar Kim Lam Chiok from Bose’s laboratory. Professors Senthil Natesan in WSU’s College of Pharmacy and Pharmaceutical Sciences and Tanya Miura in the University of Idaho’s Department of Biological Sciences served as lead collaborators. The study was supported by the National Institutes of Health and the Washington Research Foundation, and the authors declared no competing interests.

Subject of Research: Cellular signaling by extracellular ISG15 and resistance to respiratory syncytial virus

Article Title: WSU researchers discover way to ‘crank up’ the body’s antiviral defenses

Article References: WSU researchers discover way to ‘crank up’ the body’s antiviral defenses. Original publication (Bibliographic details unavailable.)

Image Credits: AI Generated

DOI: Not provided

Keywords: ISG15, respiratory syncytial virus, antiviral signaling, host-directed defense, epithelial cells, ISGylation, integrin-FAK signaling, viral infection, experimental study, Washington State University, researchers, discover

Tuft cells were first spotted by electron microscopists in the 1950s and 1960s, when researchers noticed epithelial cells bearing an unusual tuft of long microvilli unlike the shorter, uniform bristles of ordinary absorptive cells. For decades they remained a morphological curiosity, described in the airways, stomach, intestine, gallbladder and pancreas but assigned no clear function. That began to change with the arrival of genetic tools. The discovery that tuft cells express the chemosensory signaling machinery more familiar from taste buds, including the G protein gustducin and components of the transient receptor potential ion channel cascade, suggested they were the epithelial equivalent of sensory neurons, sampling the chemical environment of the gut lumen and relaying what they find to the nervous and immune systems.

Modern single-cell technologies have transformed the field again. The review highlights how transcriptomic profiling has yielded a growing panel of tuft cell biomarkers, including DCLK1, POU2F3, Trpm5, Ascl2 and the interleukin-25 receptor, allowing researchers to identify, isolate and manipulate these cells with precision that earlier generations could only dream of. These markers have revealed that tuft cells are not a monolithic population. Subsets differ across organs and along the length of the gut, expressing distinct receptor repertoires and effector molecules, which likely underlies the diverse roles the cells play in chemoreception, immune modulation, neural regulation and epithelial regeneration.

The most celebrated chapter in tuft cell biology came from studies of intestinal parasitic infection. When helminth worms colonize the intestine, tuft cells expand dramatically in number and secrete the cytokine interleukin-25, which acts on group 2 innate lymphoid cells to launch a type 2 immune response. That response, in turn, feeds back through epithelial stem cells to generate still more tuft cells, creating a feed-forward loop that amplifies host defense. This tuft cell–ILC2 circuit, now regarded as a textbook example of epithelial immune surveillance, established tuft cells as the gut’s first line of sensory detection for parasites and positioned them at the interface between epithelium and immunity.

Chemoreception, however, is only part of the story. The review emphasizes that tuft cells express a remarkable repertoire of receptors tuned to detect microbial metabolites, nutrients and danger signals. Some subsets sense short-chain fatty acids and succinate, metabolites whose concentrations shift during infection or dysbiosis. Others carry taste receptors capable of detecting bitter compounds, allowing the epithelium to respond to bacterial products. By translating luminal chemistry into neural signals through their connections with enteric nerves and into immune signals through cytokine secretion, tuft cells function as a biological transducer, converting what happens inside the gut tube into coordinated responses by the body.

In inflammatory bowel disease, the picture is more complicated and, in some ways, more provocative. Studies summarized in the review show that tuft cell abundance changes in both Crohn’s disease and ulcerative colitis, and that the cells can either restrain or amplify inflammation depending on context. Interleukin-25 production by tuft cells has been linked to tissue-protective and anti-inflammatory programs, while loss of tuft cell function has been associated with worsened colitis in experimental models. At the same time, some tuft cell–derived signals can promote inflammatory pathways under certain conditions. This duality suggests that tuft cells act as regulators of epithelial immune tone, and that therapies aimed at modulating their activity could either calm chronic inflammation or, if misapplied, worsen it.

The role of tuft cells in cancer has attracted particular attention because of one specific marker: doublecortin-like kinase 1, or DCLK1, which labels a subset of tuft cells and has become one of the most intensively studied candidates for a tumor stem cell marker in gastrointestinal malignancies. DCLK1-positive cells expand in inflamed tissue and in tumors of the stomach, pancreas and colon, and their presence has been correlated with tumor initiation, progression, metastasis and resistance to therapy in experimental systems. The review cautions that the relationship between normal tuft cells and DCLK1-positive tumor-associated cells remains incompletely resolved, but the overlap has made tuft cell lineage a focal point for research into cancer stemness and targeted therapy.

Epithelial injury and repair represent another emerging frontier. The gut lining turns over rapidly and must regenerate after damage from infection, ischemia or chemical injury. Evidence assembled in the review indicates that tuft cells participate in regenerative responses, with their numbers changing after epithelial damage and their signaling contributing to the coordination of repair programs. Because tuft cells sit at the crossroads of sensory detection, immune signaling and stem cell regulation, they may serve as an early warning system that helps the epithelium decide when and how to rebuild, a hypothesis the authors flag as a priority for future investigation.

None of this means the field has solved the tuft cell puzzle. The review is candid about the gaps: the precise developmental origins of different tuft cell subsets, the full catalog of their receptors and ligands, their exact contributions to human disease as opposed to mouse models, and the mechanisms by which they communicate with nerves, immune cells and stem cells all remain open questions. Human tissue studies are still limited by the rarity of the cells and the fragility of their morphology, and much of what is known derives from genetically manipulated mice whose tuft cell biology may not map perfectly onto patients.

Even so, the trajectory is unmistakable. A cell type once dismissed as an anatomical footnote is now implicated in some of the most burdensome gastrointestinal conditions in medicine, from parasitic infection and inflammatory bowel disease to colorectal and pancreatic cancer. The authors argue that deeper understanding of tuft cell biology could open the door to targeted clinical interventions, whether by boosting tuft cell–driven immunity against parasites, tuning their cytokine output to dampen colitis, or exploiting DCLK1 to attack therapy-resistant tumor cells. For a cell that constitutes only a sliver of the gut’s epithelial population, the tuft cell is proving that rarity is no measure of importance, and the coming years of research promise to reveal just how much influence these tiny brush-tipped sentinels exert over human digestive health.

Subject of Research: Characteristics and roles of tuft cells in gastrointestinal diseases

Article Title: Characteristics of tuft cells and their role in gastrointestinal diseases: a comprehensive narrative review

Article References: Dong, S., Zhang, T., Liu, P., & Shen, J. (2026). Characteristics of tuft cells and their role in gastrointestinal diseases: a comprehensive narrative review. Journal of Translational Medicine. https://doi.org/10.1186/s12967-026-09078-x

Image Credits: AI Generated

DOI: 10.1186/s12967-026-09078-x

Keywords: tuft cells, gastrointestinal diseases, epithelial cells, chemoreception, interleukin-25, inflammatory bowel disease, DCLK1, gastrointestinal cancer, epithelial regeneration, immune modulation, biomarkers, enteric nervous system

The study, led by Dr. Yuan Chi, Dr. Kazuko Saeki, and Professor Takehiko Yokomizo of the Juntendo University Graduate School of Medicine, was published online in the Journal of Cell Biology on September 3, 2026. The team focused on a bioactive lipid mediator known as 12-HHT, or 12S-hydroxyheptadecatrienoic acid, and its receptor BLT2, which is found primarily on epithelial cells. Their findings identify the 12-HHT/BLT2 axis as a previously unrecognized regulator of the cellular response to plasma membrane damage, opening a new chapter in the biology of wound healing at the single-cell level.

To probe how cells cope with toxin attack, the researchers worked with human lung epithelial cells, canine kidney epithelial cells, and primary mouse skin epidermal keratinocytes. By comparing cells with natural, increased, or absent BLT2 expression, they could isolate the contribution of this single receptor to membrane repair. The team then inflicted membrane damage using a battery of pore-forming agents: pneumolysin from Streptococcus pneumoniae, streptolysin O from Streptococcus pyogenes, α-hemolysin from Staphylococcus aureus, and the detergent-like molecule digitonin. This diversity of insults was deliberate. If BLT2 protected against all of them, it would suggest a general repair mechanism rather than a toxin-specific defense.

The results were striking. Cells with enhanced BLT2 signaling showed less membrane leakage, less visible structural damage, better mitochondrial health, and higher survival rates after toxin exposure. In contrast, cells lacking BLT2 were far more likely to rupture and die. The protective effect held across every damaging agent tested, including digitonin, pointing to a broadly deployed membrane-repair system rather than a narrow countermeasure against one bacterial weapon. Importantly, the researchers found that BLT2 does not prevent toxins from attaching to the cell surface in the first place. Its role begins only after the damage has been done, when the cell is fighting for its life.

The mechanism the team uncovered is elegant in its economy. When pores open in the plasma membrane, calcium ions flood into the cell from the surrounding environment. This calcium influx, long known to be a universal trigger for membrane repair, sets off the production of 12-HHT, which the researchers measured directly using liquid chromatography–mass spectrometry. The newly generated lipid then activates BLT2 on the cell surface, launching two coordinated repair actions that together rescue the wounded membrane.

The first action is a kind of cellular surgery. BLT2 signaling helps the cell pinch off damaged pieces of membrane, including the toxin pores themselves, into tiny bubbles called extracellular vesicles that are shed into the surrounding space. Electron microscopy revealed these vesicles being released from injured cells, effectively jettisoning the compromised patches of membrane along with their embedded molecular drills. This shedding strategy allows the cell to physically remove the source of the leak rather than attempting to seal each individual pore in place.

The second action rebuilds the cell’s structural integrity. BLT2 activates Rac1, a signaling protein that reorganizes actin, the fibrous scaffold that gives the cell its shape and mechanical strength. By remodeling the actin cytoskeleton, the injured cell can strengthen and reshape its damaged perimeter, contracting around the wound and supporting the membrane as it recovers. The importance of both arms of this response was confirmed by experiment: blocking either vesicle release or Rac1-driven actin remodeling eliminated BLT2’s protective effect, demonstrating that the two mechanisms work in concert rather than as redundant backups.

The experimental design behind these conclusions was rigorous and multi-layered. Beyond the cell-type comparisons and toxin panel, the team assessed membrane injury and leakage through microscopy, fluorescent dyes that report membrane integrity, lactate dehydrogenase release assays that quantify cellular leakage, and viability tests that measure survival. To dissect the mechanism, they performed experiments in calcium-free conditions, which confirmed the dependence of the pathway on calcium entry, and applied inhibitors targeting BLT2, Rac1, actin polymerization, acid sphingomyelinase, and 12-HHT production itself. Each inhibitor served as a molecular scalpel, cutting one link in the signaling chain and revealing its necessity.

The broader implications of this work extend well beyond basic cell biology. Pore-forming toxins are among the most common virulence factors produced by pathogenic bacteria, contributing to diseases ranging from pneumonia and skin infections to food poisoning. Current therapeutic strategies focus on targeting the pathogen itself, through antibiotics or antitoxin approaches. This study suggests a complementary strategy: strengthening the host. As Dr. Chi notes, in addition to targeting the pathogen or toxin, it may be possible to enhance the ability of host cells to withstand and repair membrane damage. In the long term, such host-directed therapies could help treat infectious diseases and other conditions associated with plasma membrane injury, a category that includes certain inflammatory and ischemic disorders where membrane rupture contributes to tissue damage.

The discovery also reframes how scientists think about lipid mediators. Molecules like 12-HHT are often studied in the context of inflammation, where they help recruit immune cells and coordinate tissue responses. This work shows that a lipid signal can serve as an autonomous, cell-intrinsic emergency broadcast, generated within seconds of injury and translated into immediate structural repair. The plasma membrane is often described as the cell’s first line of defense, but this research demonstrates that the defense does not end when that line is breached. Beneath the surface lies a second line, written in lipids and actin, ready to fight back the moment the barrier fails. Understanding and ultimately reinforcing that hidden repair system may one day help clinicians tip the balance in the patient’s favor during some of medicine’s most stubborn bacterial battles.

Subject of Research: The 12-HHT/BLT2 lipid signaling pathway in epithelial cell plasma membrane repair after bacterial toxin damage

Article Title: How cells fight back after bacterial toxins break through

Article References: How cells fight back after bacterial toxins break through. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: 12-HHT, BLT2 receptor, pore-forming toxins, membrane repair, epithelial cells, extracellular vesicles, Rac1, actin cytoskeleton, calcium signaling, lipid mediators, bacterial infection, Journal of Cell Biology