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

Yumeng Zhang; Pernelle Pulh; Michelle F. Pan; Yi He; Juanzhu Yan; Annie Li; Renée M. McKay; Lu Q. Le

doi:10.1172/JCI206364

¹Department of Dermatology, University of Virginia, Charlottesville, United States of America

²Department of Dermatology, University of Virginia, Virginia, United States of America

³Department of Cell Biology, University of Texas Southwestern Medical Center, Charlottesville, United States of America

Find articles by Zhang, Y. in: PubMed | Google Scholar |

¹Department of Dermatology, University of Virginia, Charlottesville, United States of America

²Department of Dermatology, University of Virginia, Virginia, United States of America

³Department of Cell Biology, University of Texas Southwestern Medical Center, Charlottesville, United States of America

Find articles by Pulh, P. in: PubMed | Google Scholar

¹Department of Dermatology, University of Virginia, Charlottesville, United States of America

²Department of Dermatology, University of Virginia, Virginia, United States of America

³Department of Cell Biology, University of Texas Southwestern Medical Center, Charlottesville, United States of America

Find articles by Pan, M. in: PubMed | Google Scholar

¹Department of Dermatology, University of Virginia, Charlottesville, United States of America

²Department of Dermatology, University of Virginia, Virginia, United States of America

³Department of Cell Biology, University of Texas Southwestern Medical Center, Charlottesville, United States of America

Find articles by He, Y. in: PubMed | Google Scholar

¹Department of Dermatology, University of Virginia, Charlottesville, United States of America

²Department of Dermatology, University of Virginia, Virginia, United States of America

³Department of Cell Biology, University of Texas Southwestern Medical Center, Charlottesville, United States of America

Find articles by Yan, J. in: PubMed | Google Scholar

¹Department of Dermatology, University of Virginia, Charlottesville, United States of America

²Department of Dermatology, University of Virginia, Virginia, United States of America

³Department of Cell Biology, University of Texas Southwestern Medical Center, Charlottesville, United States of America

Find articles by Li, A. in: PubMed | Google Scholar

¹Department of Dermatology, University of Virginia, Charlottesville, United States of America

²Department of Dermatology, University of Virginia, Virginia, United States of America

³Department of Cell Biology, University of Texas Southwestern Medical Center, Charlottesville, United States of America

Find articles by McKay, R. in: PubMed | Google Scholar

¹Department of Dermatology, University of Virginia, Charlottesville, United States of America

²Department of Dermatology, University of Virginia, Virginia, United States of America

³Department of Cell Biology, University of Texas Southwestern Medical Center, Charlottesville, United States of America

Find articles by Le, L. in: PubMed | Google Scholar |

J Clin Invest. https://doi.org/10.1172/JCI206364.
Copyright © 2026, Zhang et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Published September 22, 2026 - Version history

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 potential therapeutic targets for sebaceous gland-related diseases.

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

Yumeng Zhang,¹ Pernelle Pulh,¹ Michelle F. Pan,¹ Yi He,¹ Juanzhu Yan,³ Annie Li,¹ Renée M. McKay,¹ and Lu Q. Le¹

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

Yumeng Zhang,1 Pernelle Pulh,1 Michelle F. Pan,1 Yi He,1 Juanzhu Yan,3 Annie Li,1 Renée M. McKay,1 and Lu Q. Le1

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Yumeng Zhang,¹ Pernelle Pulh,¹ Michelle F. Pan,¹ Yi He,¹ Juanzhu Yan,³ Annie Li,¹ Renée M. McKay,¹ and Lu Q. Le¹