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Dev Cell. 2019 Nov 4;51(3):326-340.e4. doi: 10.1016/j.devcel.2019.08.015. Epub 2019 Sep 26.

Niche-Specific Factors Dynamically Regulate Sebaceous Gland Stem Cells in the Skin.

Author information

1
Department of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
2
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, Department of Epidemiology & Biostatistics, University of California, San Francisco, San Francisco, CA 94158, USA.
3
Department of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine & Bioinformatics, Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA.
4
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
5
Department of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: sunnyw@umich.edu.

Abstract

Oil-secreting sebaceous glands (SGs) are critical for proper skin function; however, it remains unclear how different factors act together to modulate SG stem cells. Here, we provide functional evidence that each SG lobe is serviced by its own dedicated stem cell population. Upon ablating Notch signaling in different skin subcompartments, we find that this pathway exerts dual counteracting effects on SGs. Suppressing Notch in SG progenitors traps them in a hybrid state where stem and differentiation features become intermingled. In contrast, ablating Notch outside of the SG stem cell compartment indirectly drives SG expansion. Finally, we report that a K14:K5→K14:K79 keratin shift occurs during SG differentiation. Deleting K79 destabilizes K14 in sebocytes, and attenuates SGs and eyelid meibomian glands, leading to corneal ulceration. Altogether, our findings demonstrate that SGs integrate diverse signals from different niches and suggest that mutations incurred within one stem cell compartment can indirectly influence another.

KEYWORDS:

K79; Krt79; epithelial stem cells; hair follicles; infundibulum; sebaceous glands; skin biology

PMID:
31564613
PMCID:
PMC6832854
[Available on 2020-11-04]
DOI:
10.1016/j.devcel.2019.08.015

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