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Cited by 606Hematopoietic Stem Cell TransplantationSingle-cell and spatial transcriptomicsAcute Myeloid Leukemia Research

Decoding human fetal liver haematopoiesis

Open access
Popescu, Dorin-Mirel, Botting, Rachel A., Stephenson, Emily, Green, Kile, Webb, Simone, Jardine, Laura, Calderbank, Emily F., Polanski, Krzysztof +48 more·2019·Nature
DOI 10.1038/s41586-019-1652-yPMC PMC6861135
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Abstract

Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 140,000 liver and 74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the influence of the tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, natural killer and innate lymphoid cell precursors in the yolk sac. We demonstrate a shift in the haemopoietic composition of fetal liver during gestation away from being predominantly erythroid, accompanied by a parallel change in differentiation potential of HSC/MPPs, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a reference for harnessing the therapeutic potential of HSC/MPPs.

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  • NR4A1/2 have been demonstrated to maintain HSC quiescence.

    “NR4A1/2 have been demonstrated to maintain HSC quiescence 32-34 .”

    From Type 1 interferon perturbates clonal competition by reshaping human blood development (2026) · cites this paper as [34]

    The Results section ('HSC/MPP differentiation potential by age'; page unavailable) reports a progressive shift toward quiescence in fetal liver HSC/MPPs, but does not link that shift to NR4A1 or NR4A2. Searches for NR4A1, NR4A1/NR4A2, and maintenance of HSC quiescence found no passage in our copy addressing the claimed role of those genes. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

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Authors
Popescu, D.-M., Botting, R. A., Stephenson, E., Green, K., Webb, S., Jardine, L., Calderbank, E. F., Polanski, K., Goh, I., Efremova, M., Acres, M., Maunder, D., Vegh, P., Gitton, Y., Park, J.-E., Vento-Tormo, R., Miao, Z., Dixon, D., Rowell, R., McDonald, D., Fletcher, J., Poyner, E., Reynolds, G., Mather, M., Moldovan, C., Mamanova, L., Greig, F., Young, M. D., Meyer, K. B., Lisgo, S., Bacardit, J., Fuller, A., Millar, B., Innes, B., Lindsay, S., Stubbington, M. J. T., Kowalczyk, M. S., Li, B., Ashenberg, O., Tabaka, M., Dionne, D., Tickle, T. L., Slyper, M., Rozenblatt-Rosen, O., Filby, A., Carey, P., Villani, A.-C., Roy, A., Regev, A., Chédotal, A., Roberts, I., Göttgens, B., Behjati, S., Laurenti, E., Teichmann, S. A., & Haniffa, M.
Affiliations
  • Newcastle University (GB)
  • Wellcome/MRC Cambridge Stem Cell Institute (GB)
  • Wellcome Sanger Institute (GB)
  • Centre National de la Recherche Scientifique (FR)
  • European Bioinformatics Institute (GB)
  • Newcastle upon Tyne Hospitals NHS Foundation Trust (GB)
  • Broad Institute (US)
  • University of Oxford (GB)
  • University of Cambridge (GB)
Corresponding author
  • Behjati, Sam
  • Laurenti, Elisa
  • Teichmann, Sarah A.
  • Haniffa, Muzlifah
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2019-10-09
Volume
574
Issue
7778
Pages
365-371
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/s41586-019-1652-y
PMC
PMC6861135
OpenAlex
W2980292232
Cited by
606
References
10
Citations by year
2026: 52 · 2025: 73 · 2024: 115 · 2023: 88 · 2022: 94 · 2021: 100 · 2020: 76 · 2019: 5 · 2018: 1
FWCI
49.48
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
  • Apollo (University of Cambridge) (submittedVersion)
  • HAL (submittedVersion, other-oa)
  • HAL (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
  • Apollo
Funders
  • European Hematology Association (TRTH118)
  • Wellcome Trust (110104/Z/15/Z, 211276/Z/18/Z, 214539/Z/18/Z, 110104, 107630/Z/15/Z, 107931/Z/15/Z, 107931, 211276, 206194)
  • National Institute for Health and Care Research (CL-2016-01-001, ACF-2017-01-009, CL-2015-01-002, ACF-2018-01-006, ACF-2019-01-004)
  • Academy of Medical Sciences (SGL015\1021)
  • Newcastle University
  • Lister Institute of Preventive Medicine
  • Medical Research Council (MC_PC_12009, MR/R006237/1, MC_PC_16040)
  • Biotechnology and Biological Sciences Research Council (BB/P002293/1)
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
Keywords
hematopoietic stem cells, multipotent progenitors, differentiation trajectories, erythropoiesis, fetal skin, yolk sac, mast cells, innate lymphoid cells, tissue microenvironment, gestational development, single-cell transcriptomics
MeSH terms
Blood Cells, Female, Fetus, Flow Cytometry, Hematopoiesis, Humans, Liver, Lymphoid Tissue, Stem Cells, Gene Expression Profiling, Single-Cell Analysis, Cellular Microenvironment

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