Cited by 1,101Hematopoietic Stem Cell TransplantationCancer, Hypoxia, and MetabolismMesenchymal stem cell research

The Distinct Metabolic Profile of Hematopoietic Stem Cells Reflects Their Location in a Hypoxic Niche

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Simsek, Tugba, Kocabas, Fatih, Zheng, Junke, DeBerardinis, Ralph J., Mahmoud, Ahmed I., Olson, Eric N., Schneider, Jay W., Zhang, Cheng Cheng +1 more·2010·Cell Stem Cell

Abstract

Bone marrow transplantation is the primary therapy for numerous hematopoietic disorders. The efficiency of bone marrow transplantation depends on the function of long-term hematopoietic stem cells (LT-HSCs), which is markedly influenced by their hypoxic niche. Survival in this low-oxygen microenvironment requires significant metabolic adaptation. Here, we show that LT-HSCs utilize glycolysis instead of mitochondrial oxidative phosphorylation to meet their energy demands. We used flow cytometry to identify a unique low mitochondrial activity/glycolysis-dependent subpopulation that houses the majority of hematopoietic progenitors and LT-HSCs. Finally, we demonstrate that Meis1 and Hif-1alpha are markedly enriched in LT-HSCs and that Meis1 regulates HSC metabolism through transcriptional activation of Hif-1alpha. These findings reveal an important transcriptional network that regulates HSC metabolism.

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Crossref · 10.1016/j.stem.2010.07.011

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  • At least some stem cell populations reside in poorly oxygenated niches.

    “at least some stem cell populations reside in poorly oxygenated niches110–112”

    From Molecular regulation of stem cell quiescence (2013) · cites this paper as [111]

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Authors
Simsek, T., Kocabas, F., Zheng, J., DeBerardinis, R. J., Mahmoud, A. I., Olson, E. N., Schneider, J. W., Zhang, C. C., & Sadek, H. A.
Affiliations
The University of Texas Southwestern Medical Center (US)
Corresponding author
  • Zhang, Cheng Cheng
  • Sadek, Hesham A.
Venue
Cell Stem Cell
Publisher
Elsevier BV
Published
2010-09
Volume
7
Issue
3
Pages
380-390
ISSN
  • 1875-9777 (ISSN-L)
  • 1934-5909
OpenAlex
W1974182237
Cited by
1,101
References
61
Citations by year
2026: 32 · 2025: 46 · 2024: 81 · 2023: 72 · 2022: 88 · 2021: 77 · 2020: 82 · 2019: 90 · 2018: 77 · 2017: 70 · 2016: 56 · 2015: 82 · 2014: 69 · 2013: 71 · 2012: 59
FWCI
35.32
Type
journal article
Language
en
Open access
Locations
  • Cell stem cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Welch Foundation
  • American Heart Association
  • National Heart, Lung, and Blood Institute (R01HL115275)
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords
long-term hematopoietic stem cells, hypoxic niche, glycolysis, mitochondrial oxidative phosphorylation, MEIS1, HIF-1α, hematopoietic progenitor cells, bone marrow transplantation
MeSH terms
Myeloid Ecotropic Viral Integration Site 1 Protein, Animals, Hypoxia, Energy Metabolism, Glycolysis, Hematopoietic Stem Cells, Mice, Inbred C57BL, Neoplasm Proteins, Transcriptional Activation, Homeodomain Proteins, Mice, Hypoxia-Inducible Factor 1, alpha Subunit, Stem Cell Niche, Metabolomics

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