Sexual dimorphism in epidermal stem cell dynamics.

October 14, 2026| Source: Nature

The epidermis is a stratified epithelium comprising proliferative basal cells and differentiated suprabasal cells that are continuously renewed throughout life. Conflicting theories have been proposed regarding the heterogeneity of the basal cell layer, with some studies proposing that all proliferative cells have self-renewal potential during homeostasis 1-5 . Meanwhile, others posit a model in which stem cell differentiation occurs through an intermediate transit-amplifying-like progenitor state with strictly limited proliferative potential 6-10 . Here, to determine the heterogeneity and pattern of cell fate, we performed intravital time-lapse imaging to track the fate of lineage-labelled cells in the skin interfollicular epidermis. Results from quantitative analyses of clonal dynamics support a two-compartment model of epidermal homeostasis, whereby basal cells are organized in a stem cell-transit-amplifying cell hierarchy. Critical to these conclusions was the discovery of sexual dimorphism in epidermal fate, with female mice showing a highly synchronized pattern of cell division, differentiation and delamination that contributes to accelerated wound healing. Single-cell RNA sequencing, transcriptional profiling and clonal analyses of castrated mice revealed that male sex hormones promote stem cell differentiation and delamination. In summary, our study provides insight into the functional identity of the stem cell population and identifies sex-specific differences in the regulation of epidermal stem cells and transit-amplifying cell fate.

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The honey bee stinger: An unusual pump with collapsible double pistons.

Most stinging animals deliver venom by contracting muscles around a venom reservoir, but honey bees employ a fundamentally different strategy. The stingers of worker bees have the unique ability to autotomize, separating from the body, to continue to sting independently. Despite more than a century of anatomical descriptions, the mechanics of venom pumping have remained unresolved due to the challenges of observing them in action. We recorded high-speed videos of active, autotomized stingers, co

Health & MedicineOctober 20, 2026

Chronic cigarette smoke exposure induces distinct stem cell states driving genetic driver-specific non-small cell lung cancer subtypes.

Cigarette smoke-induced chronic inflammation (CI) potentiates development of non-small cell lung cancer (NSCLC) by mediating genetic and epigenetic events. Using normal lung organoids (LOs), we define how chronic cigarette smoke condensate (CSC) exposure drives two separate stem cell populations to evolve premalignant states harboring progressive epigenetic and linked transcriptomic abnormalities in the absence of major driver mutations. These dynamics facilitate evolution of an immune evasive s

Health & MedicineOctober 20, 2026

Cell identity competes with surface tension to determine stromal organization in tumor spheroids beyond the CAF shell paradigm.

Cancer-associated fibroblasts (CAFs) are often found forming a peripheral stromal barrier around tumors. Here, this paradigm is challenged using microfabricated 3D cancer-CAF spheroid models combined with quantitative magnetic force tensiometry. A surface tension atlas is established for eight cancer cell lines, three CAF populations, and heterotypic tumor-CAF assemblies, spanning nearly two orders of magnitude. Surface tension is first shown to govern spheroid morphology and modulate drug respo

Health & MedicineOctober 14, 2026

Engineered TYK2 dependence enables myeloid-selective IL-10 receptor agonism.

Interleukin-10 (IL-10) is a central anti-inflammatory cytokine that suppresses immune responses in myeloid cells but can also activate T cells, limiting its therapeutic use in chronic inflammatory diseases owing to narrow efficacy windows and dose-limiting toxicities 1-5 . Here we show that myeloid and T cells differ in their dependence on JAK-family kinase pairing for IL-10 signalling and function. We took advantage of this differential kinase dependence to engineer a tetravalent nanobody-based

Health & MedicineOctober 14, 2026

Talazoparib plus enzalutamide in high-volume metastatic hormone-naive prostate cancer: a randomized phase 2 trial.

Combining inhibition of poly(ADP-ribose) polymerase and androgen receptor (AR) pathway has demonstrated clinical activity in men with metastatic prostate cancer, although the extent of benefit in tumors lacking homologous recombination repair (HRR) gene alterations remains uncertain. We conducted a randomized phase 2 trial evaluating talazoparib plus enzalutamide versus enzalutamide alone in men with high-volume metastatic hormone-naive prostate cancer (mHNPC). Fifty-four patients starting andro