The DOI matches its Crossref record; 60 of the 61 references it cites were found in a registry or an index.
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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1 retracted
Induction of Hypoxia-inducible Factor 1 Activity by Muscarinic Acetylcholine Receptor Signaling
Hirota, K., Fukuda, R., Takabuchi, S., Kizaka‐Kondoh, S., Adachi, T., Fukuda, K., & Semenza, G. L. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m405164200 · Cited by 59
RetractedWang, G. L., Jiang, B. H., Rue, E. A., & Semenza, G. L. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.12.5510 · Cited by 6,212
Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180
HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing
Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin Jr., W. G. (2001) · Science · doi:10.1126/science.1059817 · Cited by 4,735 · cited 1×
“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).”
BackgroundKim, J.-W., Tchernyshyov, I., Semenza, G. L., & Dang, C. V. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.02.002 · Cited by 3,905
Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo.
Goodell, M. A., Brose, K., Paradis, G. A., Conner, A. N., & Mulligan, R. C. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.4.1797 · Cited by 2,902
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Self-citationCellular and developmental control of O 2 homeostasis by hypoxia-inducible factor 1α
Iyer, N. V., Kotch, L. E., Agani, F., Leung, S. W., Laughner, E., Wenger, R. H., Gassmann, M., Gearhart, J. D., Lawler, A. M., Yu, A. Y., et al. (1998) · Genes & Development · doi:10.1101/gad.12.2.149 · Cited by 2,476
Zhou, S., Schuetz, J. D., Bunting, K. D., Colapietro, A.-M., Sampath, J., Morris, J. J., Lagutina, I., Grosveld, G. C., Osawa, M., Nakauchi, H., et al. (2001) · Nature Medicine · doi:10.1038/nm0901-1028 · Cited by 2,280
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Batlle, E., & Clevers, H. (2017) · Nature Medicine · doi:10.1038/nm.4409 · Cited by 2,769
Lagadinou, E. D., Sach, A., Callahan, K. P., Rossi, R. M., Neering, S. J., Minhajuddin, M., Ashton, J. M., Pei, S., Grose, V., O’Dwyer, K. M., et al. (2013) · Cell stem cell · doi:10.1016/j.stem.2012.12.013 · Cited by 1,465
Molecular regulation of stem cell quiescence
Cheung, T. H., & Rando, T. A. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3591 · Cited by 1,148
Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity
Mitroulis, I., Ruppova, K., Wang, B., Chen, L.-S., Grzybek, M., Grinenko, T., Eugster, A., Troullinaki, M., Palladini, A., Kourtzelis, I., et al. (2018) · Cell · doi:10.1016/j.cell.2017.11.034 · Cited by 1,100
Stem cell gene expression programs influence clinical outcome in human leukemia
Eppert, K., Takenaka, K., Lechman, E. R., Waldron, L., Nilsson, B., van Galen, P., Metzeler, K. H., Poeppl, A. G., Ling, V., Beyene, J., et al. (2011) · Nature Medicine · doi:10.1038/nm.2415 · Cited by 1,071
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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