A single-cell resolution developmental atlas of hematopoietic stem and progenitor cell expansion in zebrafish.
Jun Xia, Zhixin Kang, Yuanyuan Xue, Yanyan Ding, Suwei Gao, Yifan Zhang, Peng Lv, Xinyu Wang, Dongyuan Ma, Lu Wang, Jing-Dong J Han, Feng Liu
Author Information
Jun Xia: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China.
Zhixin Kang: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China.
Yuanyuan Xue: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China. ORCID
Yanyan Ding: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China.
Suwei Gao: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China.
Yifan Zhang: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China. ORCID
Peng Lv: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China.
Xinyu Wang: College of Life Sciences, University of Chinese Academy of Sciences, 100049 Beijing, China. ORCID
Dongyuan Ma: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China.
Lu Wang: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 300020 Tianjin, China. ORCID
Jing-Dong J Han: College of Life Sciences, University of Chinese Academy of Sciences, 100049 Beijing, China. ORCID
Feng Liu: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China; liuf@ioz.ac.cn. ORCID
During vertebrate embryogenesis, fetal hematopoietic stem and progenitor cells (HSPCs) exhibit expansion and differentiation properties in a supportive hematopoietic niche. To profile the developmental landscape of fetal HSPCs and their local niche, here, using single-cell RNA-sequencing, we deciphered a dynamic atlas covering 28,777 cells and 9 major cell types (23 clusters) of zebrafish caudal hematopoietic tissue (CHT). We characterized four heterogeneous HSPCs with distinct lineage priming and metabolic gene signatures. Furthermore, we investigated the regulatory mechanism of CHT niche components for HSPC development, with a focus on the transcription factors and ligand-receptor networks involved in HSPC expansion. Importantly, we identified an endothelial cell-specific G protein-coupled receptor 182, followed by in vivo and in vitro functional validation of its evolutionally conserved role in supporting HSPC expansion in zebrafish and mice. Finally, comparison between zebrafish CHT and human fetal liver highlighted the conservation and divergence across evolution. These findings enhance our understanding of the regulatory mechanism underlying hematopoietic niche for HSPC expansion in vivo and provide insights into improving protocols for HSPC expansion in vitro.
