Liu Fan, Wang Mengke, Gao Suwei, Song Gege, Liu Mengyao, Li Ying, Sun Piao, Lai Weiyi, Wang Hailin, Yang Yun-Gui, Liu Feng, Yang Ying, Wang Lu
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; Institute of Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; Sino-Danish College, University of Chinese Academy of Sciences, Beijing 100049, China.
Cell Rep. 2025 Feb 25;44(2):115324. doi: 10.1016/j.celrep.2025.115324. Epub 2025 Feb 13.
Hematopoietic stem and progenitor cells (HSPCs) undergo rapid transcriptional transitions among distinct cell states and functional properties during development, but the underlying molecular mechanism is largely unknown. Here, we characterize the mRNA mC landscape of developing HSPCs in zebrafish and found that mC modification is essential for HSPC expansion through maintaining mRNA stability. Deletion of the mC reader, Y-box binding protein 1 (Ybx1), significantly inhibits the proliferation of HSPCs in zebrafish and mice. Mechanistically, Ybx1 recognizes mC-modified mRNAs and maintains the stability of cell-cycle-related transcripts, thereby ensuring proper HSPC expansion. This study reveals the critical role of Ybx1-mediated mRNA mC modification in developmental hematopoiesis and provides new insights and epitransciptomic strategies for optimizing HSPC expansion.
造血干细胞和祖细胞（HSPCs）在发育过程中会在不同的细胞状态和功能特性之间经历快速的转录转变，但其潜在的分子机制在很大程度上尚不清楚。在这里，我们描绘了斑马鱼中发育中的HSPCs的mRNA mC图谱，并发现mC修饰通过维持mRNA稳定性对HSPCs的扩增至关重要。mC阅读器Y盒结合蛋白1（Ybx1）的缺失显著抑制了斑马鱼和小鼠中HSPCs的增殖。从机制上讲，Ybx1识别mC修饰的mRNA并维持细胞周期相关转录本的稳定性，从而确保HSPCs的正常扩增。这项研究揭示了Ybx1介导的mRNA mC修饰在发育性造血中的关键作用，并为优化HSPCs扩增提供了新的见解和表观转录组学策略。
