Tracing the first hematopoietic stem cell generation in human embryo by single-cell RNA sequencing
Authors: Lihong Bian
Yanli Ni
Zongcheng Li
Yang Zeng
Yandong Gong
Chunyu Ma
Chen Liu
Zhijie Bai
Junjie Du
Bing Liu
Yu Lan
Jian He
Journal: Cell research (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: hematopoietic stem cells; single-cell RNA sequencing; gene expression; endothelial-to-HSC transition; human embryogenesis
Affiliations: State Key Laboratory of Experimental Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100071, China., State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, 100071, China., Department of Gynecology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100071, China., 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. ., State Key Laboratory of Experimental Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100071, China. ., State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, 100071, China. ., State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, 300020, China. .

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 CD34+CD45- 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. 

Retracted: No

PubPeer comments:
 Samples used in this study were from CS 10 (23u2009dpc), CS 11 (24u2009dpc), CS 12 (27u2009dpc), CS 13 (29 and 30u2009dpc), CS 14 (32u2009dpc) and CS 15 (36u2009dpc) of **Human** embryos. Researchers can get human embryos 23 days after sex. In a natural setting, mothers would not recognize pregnancy at this stage. , 
 #1 After unprotected sex, some mothers will use the HCG Test Strip to confirm whether they are positive, and it is safer to have a drug abortion in early pregnancy. China had stopped the one-child policy since 2016 and all abortions are private and autonomous choices because they may not want colleagues or friends to know about it. ,