Gene expression data of Lin28a-positive MuSCs using RNA-seq and RIP-seq

During the early stages of embryonic development, Lin28a is expressed at high levels and gradually decreases as the embryo develops. As an RNA-binding protein, Lin28a maintains a subset of adult muscle stem cells (MuSCs) in an embryonic-like state. However, the specific mechanism for regulating RNA metabolism is not yet clear. Through the analysis of Lin28a-associated genes, we have revealed that Lin28a promotes the expression of Igf2bp3 and interacts with the Igf2bp3 protein, controlling the proliferation of MuSCs. In response to stress stimuli, Lin28a rapidly upregulates the expression of Igf2bp3, recruits mRNAs by interacting with the N6-methyladenosine (m6A) reader Igf2bp3, and forms protein complexes with G3bp1 in stress granules. Sequencing of the transcriptome and RNAs immunoprecipitated by Lin28a, Igf2bp3, and m6A antibodies in Lin28a+ MuSCs further revealed that Lin28a and Igf2bp3 collaboratively regulate the expression of DNA repair-related genes such as Fancm and Usp1 to promote DNA repair after oxidative stress. Therefore, Lin28a regulates the expression of DNA damage repair-related genes and upregulates the DNA stress response of MuSCs through stress granule regulation of m6A-modified mRNAs. This positive regulation contributes to the self-renewal of MuSCs.