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Cited by 70Hematopoietic Stem Cell TransplantationNuclear Receptors and SignalingLiver physiology and pathology

NR4A1 and NR4A3 restrict HSC proliferation via reciprocal regulation of C/EBPα and inflammatory signaling

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Freire, Pablo R., Conneely, Orla M.·2018·Blood
DOI 10.1182/blood-2017-07-795757PMC PMC5863701
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Abstract

Key Points: NR4A1/3 nuclear receptors suppress hyperproliferation and DNA damage of HSCs. NR4A1/3 act as transcriptional activators of C/EBPα while repressing a proliferative inflammatory response in HSCs.

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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 [86]

    The section titled “Nr4a1/3-null HSCs retain stem cell capacity” (page not provided) reports similar colony-forming capacity and long-term engraftment in knockout and control HSCs. The Discussion explicitly says that Nr4a1/3-null HSCs retain self-renewal capabilities, contrary to the claimed loss. (LLM, conf=0.94)

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  • NR4A1 and SOCS3 play a role in supporting HSC homeostasis by dampening inflammatory responses.

    “Both NR4A1 and SOCS3 have been noted to play a role in supporting HSC homeostasis by dampening inflammatory responses (Freire and Conneely, 2018; Kim et al., 2017).”

    From Chronic infection drives Dnmt3a-loss-of-function clonal hematopoiesis via IFNγ signaling (2021) · cites this paper as Freire and Conneely, 2018

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Cited by

Sorted by citations

Authors
Freire, P. R., & Conneely, O. M.
Affiliations
Baylor College of Medicine (US)
Venue
Blood
Publisher
American Society of Hematology
Published
2018-03-08
Volume
131
Issue
10
Pages
1081-1093
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood-2017-07-795757
PMC
PMC5863701
OpenAlex
W2784201854
Cited by
70
References
4
Citations by year
2026: 2 · 2025: 13 · 2024: 5 · 2023: 10 · 2022: 11 · 2021: 14 · 2020: 8 · 2019: 6 · 2018: 1
FWCI
5.20
Type
journal article
Language
en
Open access
Locations
  • Blood (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Dan L. Duncan Cancer Center, Baylor College of Medicine (P30 CA125123)
  • National Institutes of Health
  • National Cancer Institute (R01CA160747, CA160747, RO1 CA160747, P30CA125123)
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
Nur77, NR4A3, hematopoietic stem cells, HSC quiescence, C/EBPα, NF-κB signaling, inflammatory cytokines, HSC proliferation, transcriptional regulation, inflammation
MeSH terms
Animals, DNA Damage, DNA-Binding Proteins, Enhancer Elements, Genetic, Hematopoietic Stem Cells, Inflammation, Nerve Tissue Proteins, Receptors, Steroid, Receptors, Thyroid Hormone, Transcription, Genetic, Signal Transduction, Mice, Knockout, Oxidative Stress, CCAAT-Enhancer-Binding Proteins, Cell Proliferation, Mice, Nuclear Receptor Subfamily 4, Group A, Member 1

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