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

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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, Sadek, Hesham A.·2010·Cell Stem Cell

DOI 10.1016/j.stem.2010.07.011PMC PMC4159713

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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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Retracted
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“Hif-1a undergoes hydroxylation, followed by ubiquitination and degradation during normoxia in most cells (Ivan et al., 2001; Jaakkola et al., 2001; Kamura et al., 2000; Maxwell et al., 1999; Salceda and Caro, 1997).”
Background
HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia
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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.
ORCID: Zheng, Junke
DeBerardinis, Ralph J.
Mahmoud, Ahmed I.
Olson, Eric N.
Schneider, Jay W.
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
DOI: 10.1016/j.stem.2010.07.011
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1050 d)
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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The Distinct Metabolic Profile of Hematopoietic Stem Cells Reflects Their Location in a Hypoxic Niche

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