A 3D Atlas of Hematopoietic Stem and Progenitor Cell Expansion by Multi-dimensional RNA-Seq Analysis.

Yuanyuan Xue, Denghui Liu, Guizhong Cui, Yanyan Ding, Daosheng Ai, Suwei Gao, Yifan Zhang, Shengbao Suo, Xiaohan Wang, Peng Lv, Chunyu Zhou, Yizhou Li, Xingwei Chen, Guangdun Peng, Naihe Jing, Jing-Dong J Han, Feng Liu
Author Information
  1. Yuanyuan Xue: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, 100101 Beijing, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  2. Denghui Liu: Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  3. Guizhong Cui: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  4. Yanyan Ding: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, 100101 Beijing, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  5. Daosheng Ai: Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
  6. Suwei Gao: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
  7. Yifan Zhang: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, 100101 Beijing, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  8. Shengbao Suo: Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  9. Xiaohan Wang: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, 100101 Beijing, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  10. Peng Lv: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, 100101 Beijing, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  11. Chunyu Zhou: Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  12. Yizhou Li: Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
  13. Xingwei Chen: Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  14. Guangdun Peng: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
  15. Naihe Jing: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
  16. Jing-Dong J Han: Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: jdhan@picb.ac.cn.
  17. Feng Liu: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, 100101 Beijing, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: liuf@ioz.ac.cn.

Abstract

In vertebrates, hematopoiesis occurring in different niches is orchestrated by intrinsic and extrinsic regulators. Previous studies have revealed numerous linear and planar regulatory mechanisms. However, a multi-dimensional transcriptomic atlas of any given hematopoietic organ has not yet been established. Here, we use multiple RNA sequencing (RNA-seq) approaches, including cell type-specific, temporal bulk RNA-seq, in vivo GEO-seq, and single-cell RNA-seq (scRNA-seq), to characterize the detailed spatiotemporal transcriptome during hematopoietic stem and progenitor cell (HSPC) expansion in the caudal hematopoietic tissue (CHT) of zebrafish. Combinatorial expression profiling reveals that, in the CHT niche, HSPCs and their neighboring supporting cells are co-regulated by shared signaling pathways and intrinsic factors, such as integrin signaling and Smchd1. Moreover, scRNA-seq analysis unveils the strong association between cell cycle status and HSPC differentiation. Taken together, we report a global transcriptome landscape that provides valuable insights and a rich resource to understand HSPC expansion in an intact vertebrate hematopoietic organ.

Keywords

MeSH Term

Animals
Hematopoiesis
Hematopoietic Stem Cells
RNA-Seq
Signal Transduction
Single-Cell Analysis
Stem Cell Niche
Transcriptome
Zebrafish

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