Author
Listed:
- Fan Zhou
(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)
- Xianlong Li
(Biodynamic Optical Imaging Center, College of Life Sciences, Peking University)
- Weili Wang
(State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences)
- Ping Zhu
(Biodynamic Optical Imaging Center, College of Life Sciences, Peking University
Peking-Tsinghua Center for Life Sciences, Peking University)
- Jie Zhou
(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)
- Wenyan He
(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)
- Meng Ding
(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)
- Fuyin Xiong
(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)
- Xiaona Zheng
(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)
- Zhuan Li
(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)
- Yanli Ni
(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)
- Xiaohuan Mu
(State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences)
- Lu Wen
(Biodynamic Optical Imaging Center, College of Life Sciences, Peking University
Ministry of Education Key Laboratory of Cell Proliferation and Differentiation)
- Tao Cheng
(State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
Collaborative Innovation Center for Cancer Medicine, National Institute of Biological Sciences)
- Yu Lan
(State Key Laboratory of Proteomics, Genetic Laboratory of Development and Diseases, Institute of Biotechnology)
- Weiping Yuan
(State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences)
- Fuchou Tang
(Biodynamic Optical Imaging Center, College of Life Sciences, Peking University
Peking-Tsinghua Center for Life Sciences, Peking University
Ministry of Education Key Laboratory of Cell Proliferation and Differentiation
Center for Molecular and Translational Medicine (CMTM))
- Bing Liu
(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
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
Institute of Hematology, Medical College of Jinan University)
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.
Suggested Citation
Fan Zhou & Xianlong Li & Weili Wang & Ping Zhu & Jie Zhou & Wenyan He & Meng Ding & Fuyin Xiong & Xiaona Zheng & Zhuan Li & Yanli Ni & Xiaohuan Mu & Lu Wen & Tao Cheng & Yu Lan & Weiping Yuan & Fuchou, 2016.
"Tracing haematopoietic stem cell formation at single-cell resolution,"
Nature, Nature, vol. 533(7604), pages 487-492, May.
Handle:
RePEc:nat:nature:v:533:y:2016:i:7604:d:10.1038_nature17997
DOI: 10.1038/nature17997
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Cited by:
- Yumin Liu & Linjuan Shi & Yifan Chen & Sifan Luo & Yuehang Chen & Hongtian Chen & Wenlang Lan & Xun Lu & Zhan Cao & Zehua Ye & Jinping Li & Bo Yu & Elaine Dzierzak & Zhuan Li, 2024.
"Autophagy regulates the maturation of hematopoietic precursors in the embryo,"
Nature Communications, Nature, vol. 15(1), pages 1-17, December.
- Patrick Coulombe & Grace Cole & Amanda Fentiman & Jeremy D. K. Parker & Eric Yung & Misha Bilenky & Lemlem Degefie & Patrick Lac & Maggie Y. M. Ling & Derek Tam & R. Keith Humphries & Aly Karsan, 2023.
"Meis1 establishes the pre-hemogenic endothelial state prior to Runx1 expression,"
Nature Communications, Nature, vol. 14(1), pages 1-15, December.
- Brandon Hadland & Barbara Varnum-Finney & Stacey Dozono & Tessa Dignum & Cynthia Nourigat-McKay & Adam M. Heck & Takashi Ishida & Dana L. Jackson & Tomer Itkin & Jason M. Butler & Shahin Rafii & Cole , 2022.
"Engineering a niche supporting hematopoietic stem cell development using integrated single-cell transcriptomics,"
Nature Communications, Nature, vol. 13(1), pages 1-17, December.
- Roshana Thambyrajah & Maria Maqueda & Muhammad Zaki Fadlullah & Martin Proffitt & Wen Hao Neo & Yolanda Guillén & Marta Casado-Pelaez & Patricia Herrero-Molinero & Carla Brujas & Noemi Castelluccio & , 2024.
"IκBα controls dormancy in hematopoietic stem cells via retinoic acid during embryonic development,"
Nature Communications, Nature, vol. 15(1), pages 1-17, December.
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