Evidence map›Paper›PMID 34341490›Full record

ArticleCell research2022

Identification of HSC/MPP expansion units in fetal liver by single-cell spatiotemporal transcriptomics.

Suwei Gao, Qiang Shi, Yifan Zhang, Guixian Liang, Zhixin Kang, Baofeng Huang, Dongyuan Ma, Lu Wang, Jianwei Jiao, Xiangdong Fang and 6 more

Abstract read
In one paragraph

Article in Cell research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

63 citing papers in PubMed.

  1. Article
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  11. Article
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  15. Unveiling the crucial role of CD8Journal of translational autoimmunity · 2025
    Article
  16. HemAtlas: A Multi-omics Hematopoiesis Database.Genomics, proteomics & bioinformatics · 2025
    Article
  17. Article
  18. Article
  19. Review
  20. Article

3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Suwei Gao *State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Qiang Shi *School of Life Sciences, Center for Bioinformatics, Center for Statistical Science, Peking University, Beijing, China.ORCID http://orcid.org/0000-0003-1851-773X
Yifan ZhangState Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Guixian LiangState Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Zhixin KangState Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Baofeng HuangState Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Dongyuan MaState Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Lu WangState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
Jianwei JiaoInstitute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China.ORCID http://orcid.org/0000-0002-7893-0721
Xiangdong FangInstitute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China.
Cheng-Ran XuDepartment of Human Anatomy, Histology, and Embryology, School of Basic Medical Sciences, Peking University, Beijing, China.ORCID http://orcid.org/0000-0002-0583-4464
Longqi LiuBGI-ShenZhen, Shenzhen, Guangdong, China.
Xun XuBGI-ShenZhen, Shenzhen, Guangdong, China.ORCID http://orcid.org/0000-0002-5338-5173
Berthold GöttgensDepartment of Haematology, Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Cheng LiSchool of Life Sciences, Center for Bioinformatics, Center for Statistical Science, Peking University, Beijing, China. cheng_li@pku.edu.cn.ORCID http://orcid.org/0000-0002-1766-1409
Feng LiuState Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. liuf@ioz.ac.cn.ORCID http://orcid.org/0000-0003-3228-0943

Funding

Medical Research Council G0900951Medical Research Council MC_PC_17230Medical Research Council MR/S036113/1
6 · The paper itself

Abstract

Limited knowledge of cellular and molecular mechanisms underlying hematopoietic stem cell and multipotent progenitor (HSC/MPP) expansion within their native niche has impeded the application of stem cell-based therapies for hematological malignancies. Here, we constructed a spatiotemporal transcriptome map of mouse fetal liver (FL) as a platform for hypothesis generation and subsequent experimental validation of novel regulatory mechanisms. Single-cell transcriptomics revealed three transcriptionally heterogeneous HSC/MPP subsets, among which a CD93-enriched subset exhibited enhanced stem cell properties. Moreover, by employing integrative analysis of single-cell and spatial transcriptomics, we identified novel HSC/MPP 'pocket-like' units (HSC PLUS), composed of niche cells (hepatoblasts, stromal cells, endothelial cells, and macrophages) and enriched with growth factors. Unexpectedly, macrophages showed an 11-fold enrichment in the HSC PLUS. Functionally, macrophage-HSC/MPP co-culture assay and candidate molecule testing, respectively, validated the supportive role of macrophages and growth factors (MDK, PTN, and IGFBP5) in HSC/MPP expansion. Finally, cross-species analysis and functional validation showed conserved cell-cell interactions and expansion mechanisms but divergent transcriptome signatures between mouse and human FL HSCs/MPPs. Taken together, these results provide an essential resource for understanding HSC/MPP development in FL, and novel insight into functional HSC/MPP expansion ex vivo.

Indexed as

Endothelial CellsTranscriptomeAnimalsHematopoiesisHematopoietic Stem CellsLiverMice

Identifiers

PMID34341490
PMCPMC8724330

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.