The hair follicle is ideal for investigating stem cell regulation. This study has implications for wound healing, cancer, and hair growth. Activation of the ISR in HFSCs regulates cell fate decisions, promoting the epidermal fate over the hair follicle fate.🧵
When skin is wounded, the ISR is activated to promote re-epithelialization at the expense of hair growth. Serine deprivation potentiates the response, even activating the ISR in non-wounded skin. Ser deprivation may speed wound healing, while ISR inhibition might treat hair loss.
It's more relevant to scarring alopecias than AGA. The ISR might have a small role in AGA, but activated by an alternative pathway, such as PERK, downstream of ER stress, and independent of nutritional deficiency. There's an AGA SNP in an enhancer near LHX2 that might disrupt...
...a binding site for ISR-activated ATF3. It slightly increases the odds of severe baldness. ATF3 might even protect against AGA by repressing LHX2, which would upregulate the Wnt targets LGR5 and LEF1 in the hair germ.