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Spatiotemporal and Functional Heterogeneity of Hematopoietic Stem Cell-Competent Hemogenic Endothelial Cells in Mouse Embryos

Authors :
Yun-Qiao Li
Yandong Gong
Siyuan Hou
Tao Huang
Haizhen Wang
Di Liu
Yanli Ni
Chaojie Wang
Junliang Wang
Jun Hou
Ruichuang Yang
Jing Yan
Guangyu Zhang
Bing Liu
Yu Lan
Source :
Frontiers in Cell and Developmental Biology, Vol 9 (2021)
Publication Year :
2021
Publisher :
Frontiers Media S.A., 2021.

Abstract

Hematopoietic stem cells (HSCs) are derived from hemogenic endothelial cells (HECs) during embryogenesis. The HSC-primed HECs increased to the peak at embryonic day (E) 10 and have been efficiently captured by the marker combination CD41–CD43–CD45–CD31+CD201+Kit+CD44+ (PK44) in the aorta-gonad-mesonephros (AGM) region of mouse embryos most recently. In the present study, we investigated the spatiotemporal and functional heterogeneity of PK44 cells around the time of emergence of HSCs. First, PK44 cells in the E10.0 AGM region could be further divided into three molecularly different populations showing endothelial- or hematopoietic-biased characteristics. Specifically, with the combination of Kit, the expression of CD93 or CD146 could divide PK44 cells into endothelial- and hematopoietic-feature biased populations, which was further functionally validated at the single-cell level. Next, the PK44 population could also be detected in the yolk sac, showing similar developmental dynamics and functional diversification with those in the AGM region. Importantly, PK44 cells in the yolk sac demonstrated an unambiguous multilineage reconstitution capacity after in vitro incubation. Regardless of the functional similarity, PK44 cells in the yolk sac displayed transcriptional features different from those in the AGM region. Taken together, our work delineates the spatiotemporal characteristics of HECs represented by PK44 and reveals a previously unknown HSC competence of HECs in the yolk sac. These findings provide a fundamental basis for in-depth study of the different origins and molecular programs of HSC generation in the future.

Details

Language :
English
ISSN :
2296634X
Volume :
9
Database :
Directory of Open Access Journals
Journal :
Frontiers in Cell and Developmental Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.11130a92c15843c0ab6d24c347fee650
Document Type :
article
Full Text :
https://doi.org/10.3389/fcell.2021.699263