Telomere Dysfunction Impairs Epidermal Stem Cell Specification and Differentiation by Disrupting BMP/pSmad/P63 Signaling

The document from September 13, 2019, demonstrated that telomere dysfunction, which is associated with aging and age-related diseases, impairs epidermal stem cell specification and differentiation in skin and hair follicles by disrupting BMP/pSmad/P63 signaling. The study found that telomere shortening, caused by the loss of the Terc gene, leads to an upregulation of Follistatin (Fst), which inhibits pSmad signaling and subsequently down-regulates P63 and epidermal keratins. This occurs both in an epidermal stem cell (ESC) differentiation model and in adult mice with shortened telomeres. The underlying mechanism involves the disruption of PRC2/H3K27me3-mediated repression of Fst due to short telomeres. These findings suggest a new connection between telomere dysfunction and skin atrophy through Fst and BMP signaling, which could be targeted for developing new treatments.