Characterization of Sebaceous Gland Stem Cell Illuminates a Strategy for Maintaining Skin Oil Balance [CUT&Run]

ABSTRACT: Dry skin, caused by both environmental and lifestyle factors as well as internal factors, profoundly impacts health. Oil-producing sebaceous glands (SGs), attached to the upper portions of hair follicles, are indispensable for maintaining skin hydration, and their dysfunction has a concrete connection to dry skin. However, the cellular and molecular mechanisms underlying SG resident stem cells remain largely unknown. Here we identified transcription factor KROX20 as a novel marker of SG resident stem cells by sustaining their stemness, governing the cellular input into LRIG1-positive SG progenitors and their downstream sebocytes throughout SG morphogenesis and homeostasis. Remarkably, we observed that functional decline of SGs due to gland atrophy or ageing triggers natural resilience mechanism, manifested by autonomic regulation of the stem cell maintainer KROX20, providing a molecular illustration of the concept that ‘life finds a way’. Strikingly, we developed an inducible KROX20-positive cell ablation mouse that rapidly and robustly develops develop systemic dry flakey alopecia symptoms upon induction, named as Xeroflacia (Xero = xerosis, fla = flakey, cia = alopecia), representing a new mouse model to study the biological of dry skin and dry skin-associated alopecia. Furthermore, by characterizing genes regulated by KROX20, we unveiled that KROX20 directly modulates Notch1 transcription to orchestrate the balance between SG stem cell self-renewal and differentiation, and manipulation of Notch1 signaling provides a potential approach for topical treatment with Notch1 signaling inhibitor or activator to regulate skin oiliness and dryness. Collectively, KROX20 is indispensable for maintaining stemness of SG resident stem cells, enabling natural resilience against functional decline of SGs, and topical modulation of Krox20-Notch1 signaling offers a potential strategy to maintain skin oil balance.

ORGANISM(S): Mus musculus

PROVIDER: GSE315331 | GEO | 2026/09/01

REPOSITORIES: GEO