hnRNPA2B1 promotes osteogenesis differentiation of human adipose-derived stem cells through PHC2/GATA6/BMP axis [CUT&RUN]
m6A modification is prevalent on messenger RNA and plays a crucial role in various eukaryotic biological processes, including growth, development, disease, and aging. hnRNPA2B1, a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family, has been identified as an m6A reader. In this study, hnRNPA2B1 was shown to promote osteogenesis differentiation of human adipose-derived stem cells (hASCs) in vitro. Furthermore, the overexpression of hnRNPA2B1 facilitated bone defect healing in in vivo models of bone defects. hnRNPA2B1 RIP-seq, mRNA-seq, and MERIP-seq were used to identify PHC2 as the target gene of hnRNPA2B1. hnRNPA2B1 enhances the stability of PHC2 mRNA through m6A regulation. PHC2 binds to the promoter region of GATA6 and represses GATA6 expression by increasing H3K27me3 levels. GATA6, in turn, inhibits BMP signaling pathways and the osteogenesis differentiation of hASCs. hnRNPA2B1-PHC2-GATA6-BMP axis offers a promising perspective for the development of stem cell based bone tissue engineering. Overall design: CUT&RUN-seq was designed to identify the gene regions directly interact withPHC2. PHC2 IP gourp and IgG group were set to avoid non-specific binding.