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Nov, 2019;29 (11): 881-894.

Tracing the first hematopoietic stem cell generation in human embryo by single-cell RNA sequencing.

Yang Zeng, Jian He, Zhijie Bai, Zongcheng Li, Yandong Gong, Chen Liu, Yanli Ni, Junjie Du, Chunyu Ma, Lihong Bian, Yu Lan, Bing Liu
Author Information
  1. Yang Zeng: State Key Laboratory of Experimental Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100071, China.
  2. Jian He: State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, 100071, China.
  3. Zhijie Bai: State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, 100071, China. ORCID
  4. Zongcheng Li: State Key Laboratory of Experimental Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100071, China. ORCID
  5. Yandong Gong: State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, 100071, China.
  6. Chen Liu: State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, 100071, China.
  7. Yanli Ni: State Key Laboratory of Experimental Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100071, China.
  8. Junjie Du: State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, 100071, China.
  9. Chunyu Ma: Department of Gynecology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100071, China.
  10. Lihong Bian: Department of Gynecology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100071, China.
  11. Yu Lan: Guangzhou Regenerative Medicine and Health-Guangdong Laboratory (GRMH-GDL); Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, 510632, China. rainyblue_1999@126.com.
  12. Bing Liu: State Key Laboratory of Experimental Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100071, China. bingliu17@yahoo.com.
PMID: 31501518 DOI: 10.1038/s41422-019-0228-6

Abstract

Tracing the emergence of the first hematopoietic stem cells (HSCs) in human embryos, particularly the scarce and transient precursors thereof, is so far challenging, largely due to the technical limitations and the material rarity. Here, using single-cell RNA sequencing, we constructed the first genome-scale gene expression landscape covering the entire course of endothelial-to-HSC transition during human embryogenesis. The transcriptomically defined HSC-primed hemogenic endothelial cells (HECs) were captured at Carnegie stage (CS) 12-14 in an unbiased way, showing an unambiguous feature of arterial endothelial cells (ECs) with the up-regulation of RUNX1, MYB and ANGPT1. Importantly, subcategorizing CD34CD45 ECs into a CD44 population strikingly enriched HECs by over 10-fold. We further mapped the developmental path from arterial ECs via HSC-primed HECs to hematopoietic stem progenitor cells, and revealed a distinct expression pattern of genes that were transiently over-represented upon the hemogenic fate choice of arterial ECs, including EMCN, PROCR and RUNX1T1. We also uncovered another temporally and molecularly distinct intra-embryonic HEC population, which was detected mainly at earlier CS 10 and lacked the arterial feature. Finally, we revealed the cellular components of the putative aortic niche and potential cellular interactions acting on the HSC-primed HECs. The cellular and molecular programs that underlie the generation of the first HSCs from HECs in human embryos, together with the ability to distinguish the HSC-primed HECs from others, will shed light on the strategies for the production of clinically useful HSCs from pluripotent stem cells.

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Grants

  1. 31425012, 81890991, 31871173 and 81800102/National Natural Science Foundation of China (National Science Foundation of China)
  2. 81800102/National Natural Science Foundation of China (National Science Foundation of China)

MeSH Term

Biomarkers
Cells, Cultured
Embryo, Mammalian
Embryonic Development
Hemangioblasts
Hematopoiesis
Hematopoietic Stem Cells
Humans
RNA-Seq
Single-Cell Analysis
Transcriptome

Chemicals

Biomarkers
Journal Article

Word Cloud

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