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

• Published in: Developmental cell Vol. 51; no. 3; pp. 326 - 340.e4
• Main Authors: Veniaminova, Natalia A., Grachtchouk, Marina, Doane, Owen J., Peterson, Jamie K., Quigley, David A., Lull, Madison V., Pyrozhenko, Daryna V., Nair, Raji R., Patrick, Matthew T., Balmain, Allan, Dlugosz, Andrzej A., Tsoi, Lam C., Wong, Sunny Y.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.11.2019
• Subjects: Animals; Cell Differentiation; epithelial stem cells; Female; hair follicles; Hedgehog Proteins - metabolism; Immunoglobulin J Recombination Signal Sequence-Binding Protein - metabolism; infundibulum; K79; Keratins - metabolism; Krt79; Male; Meibomian Glands - metabolism; Mice, Knockout; Mutation - genetics; Receptors, Notch - genetics; sebaceous glands; Sebaceous Glands - cytology; Skin - cytology; skin biology; Stem Cell Niche; Stem Cells - cytology; hair follicles; skin biology; sebaceous glands; infundibulum; Krt79; epithelial stem cells; K79
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2019.08.015

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. [Display omitted] •Each sebaceous gland lobe is independently maintained by a dedicated stem cell pool•Notch directly promotes sebaceous gland stem cell differentiation into sebocytes•Notch also indirectly suppresses sebaceous gland differentiation from a distance•Keratin 79 is crucial for maintaining sebaceous and meibomian gland structural integrity Sebaceous glands secrete oils that moisturize and protect the skin. Veniaminova et al. show that sebaceous gland stem cells are both directly and indirectly regulated by Notch signaling. Furthermore, they show that proper maintenance of these glands in the skin and eyelid depends upon Keratin 79.