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Cited by 691Hematopoietic Stem Cell TransplantationMesenchymal stem cell researchDevelopmental Biology and Gene Regulation

Fate tracing reveals the endothelial origin of hematopoietic stem cells

Open access
Zovein, Ann C., Hofmann, Jennifer J., Lynch, Maureen, French, Wendy J., Turlo, Kirsten A., Yang, Yanan, Becker, Michael S., Zanetta, Lucia +4 more·2008·Cell Stem Cell
DOI 10.1016/j.stem.2008.09.018PMC PMC2631552
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Abstract

Hematopoietic stem cells (HSCs) originate within the aortic-gonado-mesonephros (AGM) region of the midgestation embryo, but the cell type responsible for their emergence is unknown since critical hematopoietic factors are expressed in both the AGM endothelium and its underlying mesenchyme. Here we employ a temporally restricted genetic tracing strategy to selectively label the endothelium, and separately its underlying mesenchyme, during AGM development. Lineage tracing endothelium, via an inducible VE-cadherin Cre line, reveals that the endothelium is capable of HSC emergence. The endothelial progeny migrate to the fetal liver, and later to the bone marrow, and are capable of expansion, self-renewal, and multilineage hematopoietic differentiation. HSC capacity is exclusively endothelial, as ex vivo analyses demonstrate lack of VE-cadherin Cre induction in circulating and fetal liver hematopoietic populations. Moreover, AGM mesenchyme, as selectively traced via a myocardin Cre line, is incapable of hematopoiesis. Our genetic tracing strategy therefore reveals an endothelial origin of HSCs.

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  • HSECs present in the early liver are derived from the hemangioblast, from which vascular endothelial cells and early hematopoietic cells are also derived.

    “HSECs present in the early liver are derived from the hemangioblast, from which vascular endothelial cells and early hematopoietic cells are also derived”

    From Single-Cell Transcriptomics Reveals Early Emergence of Liver Parenchymal and Non-parenchymal Cell Lineages (2020) · cites this paper as Zovein et al., 2008

    The Results section, “Fetal liver VE-cadherin population is migratory and does not originate in situ” (page unavailable), says the fetal-liver hematopoietic population likely migrated from the AGM. The paper traces hematopoietic cells to endothelium, but does not establish that the early-liver cells, vascular endothelial cells, and early hematopoietic cells all derive from a hemangioblast. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Inducible lineage tracing of early hemogenic sites with Cdh5-cre does not account for all hematopoietic cells within the embryo.

    “Inducible lineage tracing of early hemogenic sites with Cdh5-cre, however, does not account for all hematopoietic cells within the embryo”

    From Single-Cell Transcriptomics Reveals Early Emergence of Liver Parenchymal and Non-parenchymal Cell Lineages (2020) · cites this paper as Zovein et al., 2008

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Authors
Zovein, A. C., Hofmann, J. J., Lynch, M., French, W. J., Turlo, K. A., Yang, Y., Becker, M. S., Zanetta, L., Dejana, E., Gasson, J. C., Tallquist, M. D., & Iruela-Arispe, M. L.
Affiliations
  • University of California, Los Angeles (US)
  • The University of Texas Southwestern Medical Center (US)
  • Agilent Technologies (United States) (US)
  • University of Milan (IT)
ORCID
Venue
Cell Stem Cell
Publisher
Elsevier BV
Published
2008-12
Volume
3
Issue
6
Pages
625-636
ISSN
  • 1875-9777 (ISSN-L)
  • 1934-5909
DOI
10.1016/j.stem.2008.09.018
PMC
PMC2631552
OpenAlex
W1985299609
Cited by
691
References
1
Citations by year
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FWCI
25.68
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell stem cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • American Heart Association
  • California Institute of Regenerative Medicine
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (HL 074455, R01HL085618, R01HL074455, R01HL074257)
  • National Cancer Institute (R01CA126935, CA126935)
  • National Institute of Child Health and Human Development (K12-HD00850)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (K-12-HD 00850, K12HD000850)
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
hematopoietic stem cells, endothelial origin, lineage tracing, fetal liver, bone marrow, hematopoiesis, self-renewal, multilineage differentiation, embryonic hematopoiesis
MeSH terms
Cadherin 5, Animals, Cell Differentiation, Cell Movement, Cells, Cultured, Germ Layers, Hematopoiesis, Hematopoietic Stem Cells, Mesoderm, Mice, Transgenic, Molecular Biology, Staining and Labeling, Antigens, CD, Cadherins, Gene Expression Regulation, Developmental, Cell Lineage, Integrases, Endothelial Cells, Embryonic Development, Cell Proliferation, Mice

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