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The Distinct Metabolic Profile of Hematopoietic Stem Cells Reflects Their Location in a Hypoxic Niche
Open accessAbstract
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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“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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Metadata
- 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.
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 7
- Issue
- 3
- Pages
- 380-390
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC4159713
- 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
- bronze
- doi.org
- Licence
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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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