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Cited by 29Hematopoietic Stem Cell TransplantationNuclear Receptors and SignalingMesenchymal stem cell research

The Orphan Nuclear Receptor NR4A1 Specifies a Distinct Subpopulation of Quiescent Myeloid-Biased Long-Term HSCs

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Land, Ruben H., Rayne, Anna K., Vanderbeck, Ashley N., Barlowe, Trevor S., Manjunath, Shwetha, Gross, Matthew, Eiger, Sophie, Klein, Peter S. +4 more·2015·Stem Cells
DOI 10.1002/stem.1852PMC PMC4270858
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Abstract

Hematopoiesis is maintained throughout life by self-renewing hematopoietic stem cells (HSCs) that differentiate to produce both myeloid and lymphoid cells. The NR4A family of orphan nuclear receptors, which regulates cell fate in many tissues, appears to play a key role in HSC proliferation and differentiation. Using a NR4A1GFP BAC transgenic reporter mouse we have investigated NR4A1 expression and its regulation in early hematopoiesis. We show that NR4A1 is most highly expressed in a subset of Lin−Sca-1+c-Kit+ CD48−CD150+ long-term (LT) HSCs, and its expression is tightly associated with HSC quiescence. We also show that NR4A1 expression in HSCs is induced by PGE2, a known enhancer of stem cell engraftment potential. Finally, we find that both NR4A1GFP+ and NR4A1GFP− HSCs successfully engraft primary and secondary irradiated hosts; however, NR4A1GFP+ HSCs are distinctly myeloid-biased. These results show that NR4A1 expression identifies a highly quiescent and distinct population of myeloid-biased LT-HSCs. Stem Cells 2015;33:278–288

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  • Deletion of Nr4a1 and Nr4a3 results in loss of self-renewal of hematopoietic stem and progenitor cells.

    “Deletion of Nr4a1 and Nr4a3 resulted in loss of self-renewal of HSPCs [85,86].”

    From Clonal hematopoiesis and inflammation – the perpetual cycle (2023) · cites this paper as [85]

    The Introduction (page unavailable) reports that mice deficient in both NR4A1 and NR4A3 develop acute myeloid leukemia, while mice with reduced NR4A gene dosage show increased HSPC proliferation. It does not report that deletion of both genes causes loss of HSPC self-renewal; the Discussion links NR4A1 to quiescence and reconstitution potential but does not establish that outcome. (LLM, conf=0.84)

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Authors
Land, R. H., Rayne, A. K., Vanderbeck, A. N., Barlowe, T. S., Manjunath, S., Gross, M., Eiger, S., Klein, P. S., Cunningham, N. R., Huang, J., Emerson, S. G., & Punt, J. A.
Affiliations
  • Columbia University Irving Medical Center (US)
  • Herbert Irving Comprehensive Cancer Center (US)
  • Haverford College (US)
  • University of Pennsylvania (US)
  • Temple University (US)
Corresponding author
Punt, Jennifer A.
ORCID
Venue
Stem Cells
Publisher
Oxford University Press (OUP)
Published
2014-12-18
Volume
33
Issue
1
Pages
278-288
ISSN
  • 1066-5099 (ISSN-L)
  • 1549-4918
DOI
10.1002/stem.1852
PMC
PMC4270858
OpenAlex
W1956972180
Cited by
29
References
2
Citations by year
2026: 2 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 1 · 2015: 2
FWCI
1.42
Type
journal article
Language
en
Open access
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations
  • Stem Cells (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Science Foundation (NSF-RUI #IOS-1157986)
  • HHMI
  • Haverford College
  • NIH (1R01HL110806)
  • NCI (2R01CA090833, 5P30CA013696)
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords
Nur77, orphan nuclear receptor, hematopoietic stem cells, HSC quiescence, long-term HSCs, early hematopoiesis, prostaglandin E2, stem cell engraftment, HSC differentiation, CD48, CD150, Sca-1, CD117
MeSH terms
Animals, Cell Differentiation, Hematopoietic Stem Cells, Mice, Inbred C57BL, Cell Proliferation, Mice, Nuclear Receptor Subfamily 4, Group A, Member 1

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