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Cited by 78Hematopoietic Stem Cell TransplantationMesenchymal stem cell researchBlood disorders and treatments

Id1 Ablation Protects Hematopoietic Stem Cells from Stress-Induced Exhaustion and Aging

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Singh, Satyendra K., Singh, Shweta, Gadomski, Stephen, Sun, Lei, Pfannenstein, Alexander, Magidson, Valentin, Chen, Xiongfong, Kozlov, Serguei +3 more·2018·Cell Stem Cell
DOI 10.1016/j.stem.2018.06.001PMC PMC6149219
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Abstract

Defining mechanisms that maintain tissue stem cells during homeostasis, stress, and aging is important for improving tissue regeneration and repair and enhancing cancer therapies. Here, we show that Id1 is induced in hematopoietic stem cells (HSCs) by cytokines that promote HSC proliferation and differentiation, suggesting that it functions in stress hematopoiesis. Genetic ablation of Id1 increases HSC self-renewal in serial bone marrow transplantation (BMT) assays, correlating with decreases in HSC proliferation, mitochondrial biogenesis, and reactive oxygen species (ROS) production. Id1-/- HSCs have a quiescent molecular signature and harbor less DNA damage than control HSCs. Cytokines produced in the hematopoietic microenvironment after γ-irradiation induce Id1 expression. Id1-/- HSCs display a blunted proliferative response to such cytokines and other inducers of chronic proliferation including genotoxic and inflammatory stress and aging, protecting them from chronic stress and exhaustion. Thus, targeting Id1 may be therapeutically useful for improving HSC survival and function during BMT, chronic stress, and aging.

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  • Clusters RBC1-4 and 8 exhibited high expression of myb and id1, indicating HSC-like characteristics.

    “Clusters RBC1–4 and 8 exhibited high expression of myb and id1, indicating HSC-like characteristics (Perry et al., 2007; Singh et al., 2018; Zhang et al., 2021).”

    From Deciphering the toxic effects of polystyrene nanoparticles on erythropoiesis at single-cell resolution (2025) · cites this paper as Singh et al., 2018

    The Results section ('Id1 is induced in HSCs after bone marrow transplantation and by proinflammatory cytokines'; page unavailable) shows that HSCs can express high Id1 after cytokine stimulation. It also reports low Id1 in steady-state HSCs and higher levels in committed myeloid cells, so high Id1 alone does not establish HSC-like characteristics. The paper does not address myb expression or the RBC clusters. (LLM, conf=0.82)

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Authors
Singh, S. K., Singh, S., Gadomski, S., Sun, L., Pfannenstein, A., Magidson, V., Chen, X., Kozlov, S., Tessarollo, L., Klarmann, K. D., & Keller, J. R.
Affiliations
  • King George's Medical University (IN)
  • National Cancer Institute (US)
  • Frederick National Laboratory for Cancer Research (US)
Corresponding author
Keller, Jonathan R.
ORCID
Venue
Cell Stem Cell
Publisher
Elsevier BV
Published
2018-08
Volume
23
Issue
2
Pages
252-265.e8
ISSN
  • 1875-9777 (ISSN-L)
  • 1934-5909
DOI
10.1016/j.stem.2018.06.001
PMC
PMC6149219
OpenAlex
W2810071777
Cited by
78
References
5
Citations by year
2026: 4 · 2025: 13 · 2024: 6 · 2023: 8 · 2022: 16 · 2021: 8 · 2020: 12 · 2019: 10 · 2018: 1
FWCI
5.56
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell stem cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
Frederick National Laboratory for Cancer Research, NIH (HHSN261200800001E)
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
Keywords
Id1, hematopoietic stem cells, stem cell exhaustion, aging, stress hematopoiesis, self-renewal, mitochondrial biogenesis, reactive oxygen species, DNA damage, gamma irradiation, cytokines, hematopoietic microenvironment, HSC quiescence
MeSH terms
Aging, Animals, Cells, Cultured, Hematopoietic Stem Cells, Mice, Inbred C57BL, Stress, Physiological, Mice, Knockout, Mice, Inhibitor of Differentiation Protein 1

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