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SCD1 Modulates the Skin Homeostasis via Sustaining Hemidesmosomes

ABSTRACT: Niche for stem cells can profoundly influence the position and fate of stem cells in tissue homeostasis and associated disorders, however, the mechanisms underlying the maintenance of stem cell niche remain poorly understood. Here we report that fatty acid desaturation catabolized by stearoyl-coenzyme A desaturase 1 (SCD1) regulates the activity of hair follicle stem cells (HFSCs) via blocking the formation of the bulge, a niche for HFSCs. We further unraveled that the abnormal hair growth in mice with SCD1 deletion is due to its function in K14+ basal keratinocytes rather than directly affecting HFSCs. Mechanistically, SCD1 deficiency impaired the expression of integrin α6 and the formation of hemidesmosomes (HDs), and thus allowed the activation of FAK in K14+ keratinocytes. Activated FAK subsequently stimulated PI3K and promoted the differentiation and proliferation of these keratinocytes, resulting in downward extension of the outer root sheath (ORS) and the disruption of bulge formation. Interestingly, inhibition of PI3K signaling restored bulge formation and normalized HFSCs and hair growth. Supplementation of oleic acid, the product of SCD1, to SCD1-/- mice also enhanced HD numbers, normalized the niche of HFSCs, and promoted hair growth in SCD1-/- mice. Taken together, SCD1 is indispensable for hair growth through stabilizing the number of HDs and thus sustaining bulge formation for HFSC residence and periodic activity.

ORGANISM(S): Mus musculus

PROVIDER: GSE184346 | GEO | 2023/02/08

REPOSITORIES: GEO

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