Cited by 94Hematopoietic Stem Cell TransplantationDevelopmental Biology and Gene RegulationZebrafish Biomedical Research Applications

Lifelong haematopoiesis is established by hundreds of precursors throughout mammalian ontogeny

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Ganuza, Miguel, Hall, Trent, Finkelstein, David, Chabot, Ashley, Kang, Guolian, McKinney-Freeman, Shannon·2017·Nature Cell Biology

Abstract

Current dogma asserts that mammalian lifelong blood production is established by a small number of blood progenitors. However, this model is based on assays that require the disruption, transplantation and/or culture of embryonic tissues. Here, we used the sample-to-sample variance of a multicoloured lineage trace reporter to assess the frequency of emerging lifelong blood progenitors while avoiding the disruption, culture or transplantation of embryos. We find that approximately 719 Flk1+ mesodermal precursors, 633 VE-cadherin+ endothelial precursors and 545 Vav1+ nascent blood stem and progenitor cells emerge to establish the haematopoietic system at embryonic days (E)7-E8.5, E8.5-E11.5 and E11.5-E14.5, respectively. We also determined that the spatio-temporal recruitment of endothelial blood precursors begins at E8.5 and ends by E10.5, and that many c-Kit+ clusters of newly specified blood progenitors in the aorta are polyclonal in origin. Our work illuminates the dynamics of the developing mammalian blood system during homeostasis.

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  • The size of the HSC compartment changes dramatically during development and considerably increases in the transition into adulthood.

    “The size of the HSC compartment also changes dramatically during development, and considerably increases in the transition into adulthood (Ganuza et al., 2017; Werner et al., 2015).”

    From Unraveling Hematopoiesis through the Lens of Genomics (2020) · cites this paper as Ganuza et al., 2017

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References 56 · Cited by 94

Authors
Ganuza, M., Hall, T., Finkelstein, D., Chabot, A., Kang, G., & McKinney-Freeman, S.
Affiliations
St. Jude Children's Research Hospital (US)
Venue
Nature Cell Biology
Published
2017-09-18
Volume
19
Issue
10
Pages
1153-1163
ISSN
  • 1465-7392 (ISSN-L)
  • 1476-4679
OpenAlex
W2755845890
Cited by
94
References
56
Citations by year
2026: 4 · 2025: 11 · 2024: 22 · 2023: 15 · 2022: 8 · 2021: 8 · 2020: 16 · 2019: 5 · 2018: 4
FWCI
5.27
Type
journal article
Language
en
Open access
Locations
  • Nature Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
Funders
  • National Cancer Institute (P30CA021765)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK104028, K01DK080846)
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
Keywords
hematopoiesis, lineage tracing, polyclonal origin, dorsal aorta, mouse embryo
MeSH terms
Cadherin 5, Animals, Cell Differentiation, Cells, Cultured, Genotype, Gestational Age, Hematopoiesis, Hematopoietic Stem Cells, Luminescent Proteins, Mice, Inbred C57BL, Mice, Transgenic, Microscopy, Fluorescence, Models, Biological, Phenotype, Time Factors, Signal Transduction, Antigens, CD, Cadherins, Linear Models, Hematopoietic Stem Cell Transplantation, Gene Expression Regulation, Developmental, Coculture Techniques, Proto-Oncogene Proteins c-kit, Cell Lineage, Integrases, RNA, Untranslated, Vascular Endothelial Growth Factor Receptor-2, Endothelial Cells, Proto-Oncogene Proteins c-vav, Cell Tracking

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