Spatiotemporal and Functional Heterogeneity of Hematopoietic Stem Cell-Competent Hemogenic Endothelial Cells in Mouse Embryos
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-meson...
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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2021-08-01
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Series: | Frontiers in Cell and Developmental Biology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.699263/full |
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doaj-11130a92c15843c0ab6d24c347fee650 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 Bing Liu Bing Liu Yu Lan |
spellingShingle |
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 Bing Liu Bing Liu Yu Lan Spatiotemporal and Functional Heterogeneity of Hematopoietic Stem Cell-Competent Hemogenic Endothelial Cells in Mouse Embryos Frontiers in Cell and Developmental Biology hematopoietic stem cells hemogenic endothelial cells heterogeneity developmental hematopoiesis single-cell RNA-sequencing |
author_facet |
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 Bing Liu Bing Liu Yu Lan |
author_sort |
Yun-Qiao Li |
title |
Spatiotemporal and Functional Heterogeneity of Hematopoietic Stem Cell-Competent Hemogenic Endothelial Cells in Mouse Embryos |
title_short |
Spatiotemporal and Functional Heterogeneity of Hematopoietic Stem Cell-Competent Hemogenic Endothelial Cells in Mouse Embryos |
title_full |
Spatiotemporal and Functional Heterogeneity of Hematopoietic Stem Cell-Competent Hemogenic Endothelial Cells in Mouse Embryos |
title_fullStr |
Spatiotemporal and Functional Heterogeneity of Hematopoietic Stem Cell-Competent Hemogenic Endothelial Cells in Mouse Embryos |
title_full_unstemmed |
Spatiotemporal and Functional Heterogeneity of Hematopoietic Stem Cell-Competent Hemogenic Endothelial Cells in Mouse Embryos |
title_sort |
spatiotemporal and functional heterogeneity of hematopoietic stem cell-competent hemogenic endothelial cells in mouse embryos |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2021-08-01 |
description |
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. |
topic |
hematopoietic stem cells hemogenic endothelial cells heterogeneity developmental hematopoiesis single-cell RNA-sequencing |
url |
https://www.frontiersin.org/articles/10.3389/fcell.2021.699263/full |
work_keys_str_mv |
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doaj-11130a92c15843c0ab6d24c347fee6502021-08-11T06:57:08ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-08-01910.3389/fcell.2021.699263699263Spatiotemporal and Functional Heterogeneity of Hematopoietic Stem Cell-Competent Hemogenic Endothelial Cells in Mouse EmbryosYun-Qiao Li0Yandong Gong1Siyuan Hou2Tao Huang3Haizhen Wang4Di Liu5Yanli Ni6Chaojie Wang7Junliang Wang8Jun Hou9Ruichuang Yang10Jing Yan11Guangyu Zhang12Bing Liu13Bing Liu14Bing Liu15Yu Lan16State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, ChinaState Key Laboratory of Experimental Hematology, Fifth Medical Center of Chinese PLA General Hospital, Institute of Hematology, Beijing, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, School of Medicine, Institute of Hematology, Jinan University, Guangzhou, ChinaState Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, School of Medicine, Institute of Hematology, Jinan University, Guangzhou, ChinaPeking-Tsinghua Center for Life Sciences, Peking University, Beijing, ChinaState Key Laboratory of Experimental Hematology, Fifth Medical Center of Chinese PLA General Hospital, Institute of Hematology, Beijing, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, School of Medicine, Institute of Hematology, Jinan University, Guangzhou, ChinaDepartment of Radiotherapy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaThe Fifth Medical Center of PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, ChinaThe Fifth Medical Center of PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, ChinaState Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, ChinaState Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, ChinaState Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, ChinaState Key Laboratory of Experimental Hematology, Fifth Medical Center of Chinese PLA General Hospital, Institute of Hematology, Beijing, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, School of Medicine, Institute of Hematology, Jinan University, Guangzhou, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, School of Medicine, Institute of Hematology, Jinan University, Guangzhou, ChinaHematopoietic 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.https://www.frontiersin.org/articles/10.3389/fcell.2021.699263/fullhematopoietic stem cellshemogenic endothelial cellsheterogeneitydevelopmental hematopoiesissingle-cell RNA-sequencing |