N6-Methyladenosine (m6A)-circHECA Recruiting FUS Promotes Differentiation of SHF Stem Cells into Hair Follicle Lineages Through Stabilizing FOXM1 mRNA to Activate NOTCH Pathway in Cashmere Goats.

Cashmere goats are widely distributed in the cold, arid and semi-arid remote regions of northern China. Their main economic value is the production of precious cashmere fibers. The differentiation of second hair follicle (SHF) stem cells into hair follicle lineages plays a crucial role in SHF regeneration as well as in the morphogenesis and growth of cashmere fibers; however, its precise molecular mechanism is still unclear. In this study, we found that N6-methyladenosine (m6A)-circHECA recruiting FUS promoted the differentiation of SHF stem cells into hair follicle lineages through stabilizing FOXM1 mRNA in SHF stem cells, thereby activating the NOTCH pathway in cashmere goats. Furthermore, we confirmed that the m6A modification of circHECA is required for the FUS/FOXM1-mediated NOTCH signaling pathway to facilitate the differentiation of SHF stem cells into hair follicle lineages via transfecting circHECA m6A-deficient mutants. Our results contribute to elucidating the functional mechanism of m6A-circHECA in the differentiation of SHF stem cells into hair follicle lineages in cashmere goats.