Divergent expression of Neurl3 from hemogenic endothelial cells to hematopoietic stem progenitor cells during development

Xiaowei Ning; Junjie Du; Yandong Gong; Yingpeng Yao; Zhijie Bai; Yanli Ni; Yanyan Li; Zongcheng Li; Haixin Zhao; Jie Zhou; Bing Liu; Yu Lan; Siyuan Hou

doi:10.1016/j.jgg.2023.05.006

Volume 50 Issue 9

Sep. 2023

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Article Navigation > Journal of Genetics and Genomics > 2023 > 50(9): 661-675

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Divergent expression of Neurl3 from hemogenic endothelial cells to hematopoietic stem progenitor cells during development

doi: 10.1016/j.jgg.2023.05.006 cstr: 32370.14.j.jgg.2023.05.006

a. State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China;
b. Chinese PLA Medical School, Chinese PLA General Hospital, Beijing 100853, China;
c. State Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Institute of Hematology, Senior Department of Hematology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, China;
d. Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, China

Funds:

This work was supported by the National Key R&D Program of China (2022YFA1103501, 2020YFA0112400, 2021YFA1100102), the National Natural Science Foundation of China (82000111, 81890991, 31930054, 82200121, 82122004, 82270118), and the Program for Guangdong Introducing Innovative and Entrepreneurial Teams (2017ZT07S347).

Received Date: 2023-02-13
Accepted Date: 2023-05-15
Rev Recd Date: 2023-05-07
Publish Date: 2023-05-23

Abstract

Abstract

Prior to the generation of hematopoietic stem cells (HSCs) from the hemogenic endothelial cells (HECs) mainly in the dorsal aorta in midgestational mouse embryos, multiple hematopoietic progenitors including erythro-myeloid progenitors and lymphoid progenitors are generated from yolk sac HECs. These HSC-independent hematopoietic progenitors have recently been identified as major contributors to functional blood cell production until birth. However, little is known about yolk sac HECs. Here, combining integrative analyses of multiple single-cell RNA-sequencing datasets and functional assays, we reveal that Neurl3-EGFP, in addition to marking the continuum throughout the ontogeny of HSCs from HECs, can also serve as a single enrichment marker for yolk sac HECs. Moreover, while yolk sac HECs have much weaker arterial characteristics than either arterial endothelial cells in the yolk sac or HECs within the embryo proper, the lymphoid potential of yolk sac HECs is largely confined to the arterial-biased subpopulation featured by the Unc5b expression. Interestingly, the B lymphoid potential of hematopoietic progenitors, but not for myeloid potentials, is exclusively detected in Neurl3-negative subpopulations in midgestational embryos. Taken together, these findings enhance our understanding of blood birth from yolk sac HECs and provide theoretical basis and candidate reporters for monitoring step-wise hematopoietic differentiation.
- Neurl3-EGFP,
- Yolk sac,
- Hematopoietic progenitors,
- Hemogenic endothelial cells,
- Single-cell RNA-Sequencing,
- Lymphoid potential

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References(46)

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