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Peer-reviewedCC BY 4.0The Journal of Clinical Investigation

KROX20 marks sebaceous gland stem cells and regulates their differentiation to maintain skin oil balance

  • Yumeng Zhang1
  • Pernelle Pulh1
  • Michelle F. Pan1
  • Yi He1
  • Juanzhu Yan2
  • Annie Li1
  • Renée M. McKay1
  • Lu Q. Le1
  1. 1Department of Dermatology, University of Virginia, Charlottesville, Virginia, USA.
  2. 2Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
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Abstract

Oil-producing sebaceous glands (SGs), attached to the upper/middle portion of hair follicles, are indispensable for maintaining skin hydration, and their dysfunction leads to dry skin. However, the molecular mechanisms underlying regulation of SG stem cells remain largely unknown. We identified transcription factor KROX20 as a marker of SG stem cells that sustains their stemness throughout SG morphogenesis and homeostasis. We developed an inducible mouse model in which ablation of KROX20-positive cells causes SG loss and rapidly and robustly induces dry, flaky, alopecia symptoms following induction. This model, termed xeroflacia (xero = xerosis, fla = flaky, cia = alopecia), provides a tool for studying the biology of dry skin. Furthermore, we found that KROX20 directly regulates Notch1 transcription to orchestrate the balance between SG stem cell self-renewal and differentiation. Small molecule drug modulation of Notch1 signaling to activate or inhibit the pathway enabled us to regulate SG differentiation to maintain skin oil levels, providing a proof of principle that other signaling pathways downstream of Krox20 could be therapeutic targets for SG-related diseases.

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Cite

BibTeXRIS
BibTeX
@article{zhang2026krox20,
  title = {{KROX20 marks sebaceous gland stem cells and regulates their differentiation to maintain skin oil balance}},
  author = {Yumeng Zhang and Pernelle Pulh and Michelle F. Pan and Yi He and Juanzhu Yan and Annie Li and Renée M. McKay and Lu Q. Le},
  journal = {The Journal of Clinical Investigation},
  year = {2026},
  month = sep,
  doi = {10.1172/jci206364},
  url = {https://doi.org/10.1172/jci206364},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - KROX20 marks sebaceous gland stem cells and regulates their differentiation to maintain skin oil balance
AU  - Yumeng Zhang
AU  - Pernelle Pulh
AU  - Michelle F. Pan
AU  - Yi He
AU  - Juanzhu Yan
AU  - Annie Li
AU  - Renée M. McKay
AU  - Lu Q. Le
PY  - 2026
DA  - 2026/09/22
JO  - The Journal of Clinical Investigation
DO  - 10.1172/jci206364
UR  - https://doi.org/10.1172/jci206364
AB  - Oil-producing sebaceous glands (SGs), attached to the upper/middle portion of hair follicles, are indispensable for maintaining skin hydration, and their dysfunction leads to dry skin. However, the molecular mechanisms underlying regulation of SG stem cells remain largely unknown. We identified transcription factor KROX20 as a marker of SG stem cells that sustains their stemness throughout SG morphogenesis and homeostasis. We developed an inducible mouse model in which ablation of KROX20-positive cells causes SG loss and rapidly and robustly induces dry, flaky, alopecia symptoms following induction. This model, termed xeroflacia (xero = xerosis, fla = flaky, cia = alopecia), provides a tool for studying the biology of dry skin. Furthermore, we found that KROX20 directly regulates Notch1 transcription to orchestrate the balance between SG stem cell self-renewal and differentiation. Small molecule drug modulation of Notch1 signaling to activate or inhibit the pathway enabled us to regulate SG differentiation to maintain skin oil levels, providing a proof of principle that other signaling pathways downstream of Krox20 could be therapeutic targets for SG-related diseases.
SN  - 0021-9738
SN  - 1558-8238
ER  -