Distinct types of stem cell divisions determine organ regeneration and aging in hair follicles

Aging organs functionally and structurally decline with the loss of their regenerative capabilities, yet the existence of distinct cell division programs that determine organ fates is unknown. Hair follicles, mammalian mini-organs that grow hair, miniaturize by aging. Here we report that hair follicle regeneration and aging are driven by distinct cell division types of hair follicle stem cells (HFSCs). Cell fate tracing and cell division axis analysis in mice revealed that HFSCs undergo symmetric and asymmetric cell divisions to generate a new bulge, yet preferentially provoke “stress-responsive type” asymmetric cell divisions that generate aberrantly differentiating cells upon age/stress. That dynamic program with repetitive divisions efficiently eradicates those cells through defective association and stabilization of a hemidesmosomal protein COL17A1 and a cell-polarity-protein aPKCλ in HFSCs, thereby causing organ aging. The forced stabilization of COL17A1 rescued organ aging through aPKCλ stabilization. These results demonstrate that distinct cell division programs govern tissue/organ fates. Hair follicle stem cells (HFSCs) and Interfollicular epidermis (IFE) from young/aged Col17a1, aPKCλ cKO and young/aged COL17A1 transgenic mice were FACS isolated and RNA was extracted before being hybridized Agillent microarray. We obtained a gene of list by comparing Young/Aged, Col17a1/aPKCλ cKO and young/aged COL17A1 transgenic mice.