REVIEW article
Front. Cell Dev. Biol.
Sec. Stem Cell Research
Unraveling Hematopoietic Stem Cell Ontogeny through Single-Cell Multi-Omics Approaches
Provisionally accepted
- Shandong Second Medical University, Weifang, China
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Definitive hematopoietic stem cells (HSCs) originate de novo within the vertebrate aorta-gonad-mesonephros (AGM) region via endothelial-to-hematopoietic transition (EHT) from hemogenic endothelial cells (HECs). The application of single-cell multi-omics has significantly deepened our knowledge about hematopoietic development. In this review, we focus on the ontogeny of HSCs and summarize novel insights gained from single-cell omics studies. These include newly identified components of hematopoietic regulatory networks, the cellular heterogeneity during HSC generation, innovative strategies for enriching rare cell subpopulations, and newfound knowledge about the AGM microenvironment. In the concluding section, we discuss key unresolved questions related to in vivo generation and in vitro induction of HSCs, while exploring the potential of single-cell omics to propel future research in this field.
Keywords: Hematopoietic stem cells (HSCS), Single-cell multi-omics, endothelial-to-hematopoietic transition (EHT), aorta-gonad-mesonephros (AGM) region, Developmental heterogeneity
Received: 14 Sep 2025; Accepted: 30 Oct 2025.
Copyright: © 2025 Li, Jia, Huo, Wu and Song. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Mei Li, limei@sdsmu.edu.cn
Ningning Song, songningning@sdsmu.edu.cn
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