An epitranscriptomic program maintains skeletal stem cell quiescence via a METTL3-FEM1B-GLI1 axis.

ABSTRACT: Skeletal stem cells (SSCs) maintain the skeletal system via pluripotency and differentiation capacity. However, it remains largely unknown how these cells precisely regulate their function to maintain skeletal organization. Here, we delineate the RNA m⁶A modification landscape across skeletal cell populations in the mouse epiphysis. Our findings show that m⁶A modifications are prevalent in skeletal stem cell and progenitor populations and play critical roles in cell fate determination. Genetic deletion of Mettl3, the core catalytic subunit of the m⁶A-methyltransferase complex, in murine skeletal stem and progenitors impaired bone development, leading to shortened limbs, disrupted growth plate zonation, and decreased bone mass. Moreover, Mettl3 deficiency in

SUBMITTER: Wang J 

PROVIDER: S-EPMC12000498 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature