RNA m5C methylation mediated by Ybx1 ensures hematopoietic stem and progenitor cell expansion
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 m<sup>5</sup>C landscape of developing HSPCs in zebrafish and found that m<sup>5</sup>C modification is essential for HSPC expansion through maintaining mRNA stability. Deletion of the m<sup>5</sup>C reader, Y-box binding protein 1 (Ybx1), significantly inhibits the proliferation of HSPCs in zebrafish and mice. Mechanistically, Ybx1 recognizes m<sup>5</sup>C-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 m<sup>5</sup>C modification in developmental hematopoiesis and provides new insights and epitransciptomic strategies for optimizing HSPC expansion.
Authors
- Weiyi Lai (ORCID: https://orcid.org/0000-0002-8010-2490)
- Ying Yang (ORCID: https://orcid.org/0000-0002-8104-5985)
- Yun‐Gui Yang (ORCID: https://orcid.org/0000-0002-2821-8541)
- Gege Song (ORCID: https://orcid.org/0000-0002-6556-1840)
- Lu Wang (ORCID: https://orcid.org/0000-0003-4788-3237)
- Fan Liu (ORCID: https://orcid.org/0000-0002-9481-0797)
- Ying Li (ORCID: https://orcid.org/0000-0002-3308-906X)
- Feng Liu (ORCID: https://orcid.org/0000-0003-3228-0943)
- Ping Sun
- Mengke Wang (ORCID: https://orcid.org/0000-0001-5361-0986)
- Mengyao Liu (ORCID: https://orcid.org/0000-0002-3695-6341)
- Hailin Wang (ORCID: https://orcid.org/0000-0002-1843-999X)
- Suwei Gao
Institutions
- Shandong University (CN)
- Chinese Academy of Sciences (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Beijing Institute of Genomics (CN)
- Research Center for Eco-Environmental Sciences (CN)
- Institute of Hematology & Blood Diseases Hospital (CN)
- Institute of Zoology (CN)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-02-01
- DOI
- https://doi.org/10.1016/j.celrep.2025.115324
- Citations
- 5
- Primary Topic
- RNA modifications and cancer
- Type
- article
- Field-Weighted Citation Impact
- 4.03
Funders
- National Natural Science Foundation of China
- National Key Research and Development Program of China
- Youth Innovation Promotion Association
- Science Fund for Distinguished Young Scholars of Tianjin