期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2015748118
关键词
zebrafish; HSPC expansion; single-cell RNA-seq; caudal hematopoietic tissue; Gpr182
资金
- National Key Research and Development Program of China [2018YFA0800200, 2018YFA0801000, 2016YFA0100500]
- Strategic Priority Research Program of the Chinese Academy of Sciences, China [XDA16010207]
- National Natural Science Foundation of China [31830061, 81530004, 31425016]
- Youth Innovation Promotion Association Chinese Academy of Sciences (CAS) [2016083]
Single-cell RNA sequencing was used to decipher the developmental landscape of zebrafish caudal hematopoietic tissue, revealing distinct heterogeneous HSPCs with lineage priming and metabolic gene signatures. The study identified an endothelial cell-specific G protein-coupled receptor 182 as evolutionarily conserved in supporting HSPC expansion in both zebrafish and mice, highlighting the conservation and divergence across evolution between zebrafish CHT and human fetal liver.
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.
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