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  3. DNA methyltransferase Dnmt3ba-mediated epigenetic modulation of Integrin signaling is essential for hematopoietic stem and progenitor cell development

DNA methyltransferase Dnmt3ba-mediated epigenetic modulation of Integrin signaling is essential for hematopoietic stem and progenitor cell development

  • Commun Biol. 2025 Nov 19;8(1):1612. doi: 10.1038/s42003-025-09003-w.
Kang Ai # 1,  Yue Wu # 1,  Guixian Liang # 2,  Haotian Kong 1,  Xuening Yang 1,  Na Li 1,  Ziting Liu 1,  Yijie Dong 1,  Junjie Xu 1,  Li Zhang 1,  Xiuli Chen 1,  Yuanyuan Fu 1,  Lu Wang 3,  Lei Li 4
Affiliations

Affiliations

  • 1 Key Laboratory of Experimental Teratology of the Ministry of Education, Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
  • 2 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, China.
  • 3 State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. [email protected].
  • 4 Key Laboratory of Experimental Teratology of the Ministry of Education, Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China. [email protected].
  • # Contributed equally.
PMID: 41261168 DOI: 10.1038/s42003-025-09003-w
Abstract

In vertebrate embryonic development, hematopoietic stem and progenitor cells (HSPCs) originate from a subset of arterial endothelial cells in the ventral wall of the dorsal aorta through endothelial-to-hematopoietic transition (EHT). Despite extensive research efforts, gaps persist in understanding the establishment of HSPC development. In this study, we demonstrate that DNA Methyltransferase 3ba (Dnmt3ba), highly expressed in the hemogenic endothelial cells (HECs), plays a crucial role in regulating HEC survival in zebrafish. Dnmt3ba deficiency leads to hypomethylation at the itgα3b and itgα7 loci, diminishing the expression of these Integrins and downstream Akt signaling and MDM2 phosphorylation, while concurrently triggering HEC Apoptosis by upregulation of P53 activity. Manipulation of DNMT3B in an iPSC-derived human hematopoietic differentiation system indicates functional conservation. Collectively, our findings unveil an epigenetic mechanism governed by Dnmt3ba, orchestrating HEC survival through epigenetic modulation of Integrin signaling.

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