ИСТИНА

Hair follicle (HF) cyclic transformations are accompanied by changes in cell behavior and metabolism. Nevertheless, it is not clear how self-renewal, proliferation, and differentiation are related to activity of adaptive factors such as HIF1 (HIF1a/ARNT heterodimer). By mapping nuclear localization of HIF1a/ARNT to different cell identities during HF cycle, we delineate a follicle cell fate scenario in which state transitions are determined by a “landscape” of HIF1a/ARNT expression. Telogen is characterized by a lack of HIF1a in the bulge and in papilla-adjacent epithelial cells. ARNT is high in the later but low in bulge. Anagen entry is marked by increase of HIF1a and ARNT in germinative zone while bulge remains negative. Wave-like HF cell activation/growth (Ki67+) shadows the upward propagation of HIF1a/ARNT in lower HF. In stationary anagen, the upper ORS remains HIF1a-negative but ARNT-positive. The acquisition of IRS and hair shaft cell fates is associated with retention of ARNT-positivity and downregulation of HIF1a. In catagen, HIF1a in lower ORS and in the matrix declines, while some cells of germinative layer (which are likely to acquire germ cell fate in telogenr) retain ARNT+. We propose that life history of an ordinary follicular keratinocyte starting from quiescent uncommitted state (HIF1alow/ARNTlow/a6-integrin+) through committed ORS or germinative cell states (HIF1alow/ARNThigh/a6-integrin+) then to proliferating cells of the matrix and lower ORS (HIF1ahigh/ARNThigh) and finally to differentiating cells of IRS and precortex (HIF1alow/ARNThigh/a6-integrin-) is unfolded in a “landscape of HIF1a/ARNT activity”, which serves as a framework for coordination between cell metabolism, behavior, and identity.