A single-cell resolution developmental atlas of hematopoietic stem and progenitor cell expansion in zebrafish
In: Proceedings of the National Academy of Sciences of the United States of America, Jg. 118 (2021-03-31), Heft 14
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Significance The caudal hematopoietic tissue (CHT) is characterized as a hematopoietic organ for fetal hematopoietic stem and progenitor cell (HSPC) expansion in zebrafish. In this study, we used scRNA-seq combined with functional assays to decode the developing CHT. First, we resolved fetal HSPC heterogeneity, manifested as lineage priming and metabolic gene signatures. We further analyzed the cellular interactions among nonhematopoietic niche components and HSPCs and identified an endothelial cell-specific factor, Gpr182, followed by experimental validation of its role in promoting HSPC expansion. Finally, we uncovered the conservation and divergence of developmental hematopoiesis between human fetal liver and zebrafish CHT. Our study provides a valuable resource for fetal HSPC development and clues to establish a supportive niche for HSPC expansion in vitro.
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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A single-cell resolution developmental atlas of hematopoietic stem and progenitor cell expansion in zebrafish
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Autor/in / Beteiligte Person: | Liu, Feng ; Xia, Jun ; Han, Jing-Dong J. ; Wang, Xinyu ; Kang, Zhixin ; Gao, Suwei ; Zhang, Yifan ; Lv, Peng ; Ma, Dongyuan ; Wang, Lu ; Ding, Yanyan ; Xue, Yuanyuan |
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Zeitschrift: | Proceedings of the National Academy of Sciences of the United States of America, Jg. 118 (2021-03-31), Heft 14 |
Veröffentlichung: | 2021 |
Medientyp: | unknown |
ISSN: | 1091-6490 (print) |
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