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  3. RNA m5C methylation mediated by Ybx1 ensures hematopoietic stem and progenitor cell expansion

RNA m5C methylation mediated by Ybx1 ensures hematopoietic stem and progenitor cell expansion

  • Cell Rep. 2025 Feb 25;44(2):115324. doi: 10.1016/j.celrep.2025.115324.
Fan Liu 1,  Mengke Wang 2,  Suwei Gao 3,  Gege Song 2,  Mengyao Liu 1,  Ying Li 1,  Piao Sun 1,  Weiyi Lai 4,  Hailin Wang 4,  Yun-Gui Yang 5,  Feng Liu 6,  Ying Yang 7,  Lu Wang 8
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao 266237, China.
  • 4 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
  • 5 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. Electronic address: ygyang@big.ac.cn.
  • 6 Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao 266237, China; State Key Laboratory of Membrane Biology, Institute of Zoology, Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing 100101, China. Electronic address: liuf@sdu.edu.cn.
  • 7 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. Electronic address: yingyang@big.ac.cn.
  • 8 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; Tianjin Institutes of Health Science, Tianjin 301600, China. Electronic address: wanglu1@ihcams.ac.cn.
PMID: 39954256 DOI: 10.1016/j.celrep.2025.115324
Abstract

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 m5C landscape of developing HSPCs in zebrafish and found that m5C modification is essential for HSPC expansion through maintaining mRNA stability. Deletion of the m5C reader, Y-box binding protein 1 (Ybx1), significantly inhibits the proliferation of HSPCs in zebrafish and mice. Mechanistically, Ybx1 recognizes m5C-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 m5C modification in developmental hematopoiesis and provides new insights and epitransciptomic strategies for optimizing HSPC expansion.

Keywords

5-methylcytosine; CP: Stem cell research; Ybx1; cell-cycle progression; hematopoietic stem and progenitor cells; mRNA stability.

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