Cell Stem Cell：同济大学高亚威/高绍荣/王译萱团队揭示m⁶A修饰限制人类胚胎干细胞全能性的机制

Core Insights - The study reveals that m6A modification regulates LTR silencing through an L1PA RNA-mediated transcriptional regulatory network, limiting the totipotency of naive human embryonic stem cells [3][5] - The research highlights the molecular connection between RNA modifications and chromatin remodeling [3] Group 1: Key Findings - METTL3 deficiency allows naive human embryonic stem cells (hESC) to regain totipotency, activating the 8-cell transcriptional program [5][6] - Removal of m6A modification on L1PA activates 8-cell LTRs and induces naive hESCs into an 8-cell-like state [6] - m6A regulates the recruitment preferences of EP300 and KAP1 in the L1PA scaffold complex [6] Group 2: Mechanistic Insights - L1PA interacts with 8-cell LTRs and eRNA sites, forming different chromatin states through m6A [6] - The study uncovers a conserved mechanism where species-specific LINE-1 subfamily m6A modifications regulate LTR activity, emphasizing the role of transposons in RNA-chromatin interactions during cell fate transitions [9]