Tracing haematopoietic stem cell formation at single-cell resolution
Authors: Xianlong Li
Fan Zhou
Yanli Ni
Ping Zhu
Weiping Yuan
Weili Wang
Wenyan He
Jie Zhou
Yu Lan
Meng Ding
Tao Cheng
Zhuan Li
Fuyin Xiong
Fuchou Tang
Xiaona Zheng
Lu Wen
Xiaohuan Mu
Bing Liu
Journal: Nature (2016)
Discipline: Multidisciplinary
Keywords: Haematopoietic stem cells; pre-HSCs; single-cell RNA sequencing; transcriptional machinery; mechanistic targets of rapamycin (mTOR)
Affiliations: State Key Laboratory of Proteomics, Translational Medicine Center of Stem Cells, 307-Ivy Translational Medicine Center, Laboratory of Oncology, Affiliated Hospital, Academy of Military Medical Sciences, Beijing 100071, China., Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, China., State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin 300020, China., Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China., Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China., Collaborative Innovation Center for Cancer Medicine, National Institute of Biological Sciences, Tianjin 300020, China., State Key Laboratory of Proteomics, Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing 100071, China., Center for Molecular and Translational Medicine (CMTM), Beijing 100101, China., Institute of Hematology, Medical College of Jinan University, Guangzhou 510632, China.

Abstract:  Haematopoietic stem cells (HSCs) are derived early from embryonic precursors, such as haemogenic endothelial cells and pre-haematopoietic stem cells (pre-HSCs), the molecular identity of which still remains elusive. Here we use potent surface markers to capture the nascent pre-HSCs at high purity, as rigorously validated by single-cell-initiated serial transplantation. Then we apply single-cell RNA sequencing to analyse endothelial cells, CD45(-) and CD45(+) pre-HSCs in the aorta-gonad-mesonephros region, and HSCs in fetal liver. Pre-HSCs show unique features in transcriptional machinery, arterial signature, metabolism state, signalling pathway, and transcription factor network. Functionally, activation of mechanistic targets of rapamycin (mTOR) is shown to be indispensable for the emergence of HSCs but not haematopoietic progenitors. Transcriptome data-based functional analysis reveals remarkable heterogeneity in cell-cycle status of pre-HSCs. Finally, the core molecular signature of pre-HSCs is identified. Collectively, our work paves the way for dissection of complex molecular mechanisms regulating stepwise generation of HSCs in vivo, informing future efforts to engineer HSCs for clinical applications. 

Retracted: No

PubPeer comments:
 Extended data Figure 5 appears to have a duplicated panel. Brought to my attention by another reader. *** ![file] , 
 We very much thank the readeru2019s kind reminding. With carefully checking the raw data in originally published Supplementary Table 9 (which is related to the mentioned panel and presented correctly), we found that this duplicated panel in Extended Data Figure 5b (Glycolysis Gluconeogenesis) was a unconscious mistake during picture processing. The corrected information has already been uploaded on the GitHub at https: github.com Liu-Lan-lab Correction-Zhou-et-al.-Nature.-2016. , 
 We very much thank the readeru2019s kind reminding. With carefully checking the raw data in originally published Supplementary Table 9 (which is related to the mentioned panel and presented correctly), we found that this duplicated panel in Extended Data Figure 5b (Glycolysis Gluconeogenesis) was a unconscious mistake during picture processing. The corrected information has already been uploaded on the GitHub at https: github.com Liu-Lan-lab Correction-Zhou-et-al.-Nature.-2016. ,