The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Restraining Lysosomal Activity Preserves Hematopoietic Stem Cell Quiescence and Potency
Open accessAbstract
SUMMARY Quiescence is a fundamental property that maintains hematopoietic stem cell (HSC) potency throughout life. Quiescent HSCs are thought to rely on glycolysis for their energy, but the overall metabolic properties of HSCs remain elusive. Using combined approaches, including single-cell RNA sequencing (RNA-seq), we show that mitochondrial membrane potential (MMP) distinguishes quiescent from cycling-primed HSCs. We found that primed, but not quiescent, HSCs relied readily on glycolysis. Notably, in vivo inhibition of glycolysis enhanced the competitive repopulation ability of primed HSCs. We further show that HSC quiescence is maintained by an abundance of large lysosomes. Repression of lysosomal activation in HSCs led to further enlargement of lysosomes while suppressing glucose uptake. This also induced increased lysosomal sequestration of mitochondria and enhanced the competitive repopulation ability of primed HSCs by over 90-fold in vivo. These findings show that restraining lysosomal activity preserves HSC quiescence and potency and may be therapeutically relevant.
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Cited by
Lysosome biogenesis: Regulation and functions
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Cellular Mechanisms and Regulation of Quiescence
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TFEB-mediated endolysosomal activity controls human hematopoietic stem cell fate
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PU.1 enforces quiescence and limits hematopoietic stem cell expansion during inflammatory stress
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“, 2011), organelle homeostasis mechanisms (Hinge et al., 2020; Liang et al., 2020), and signals generated from the bone marrow (BM) niche (Morrison and Scadden, 2014).”
BackgroundMetabolic regulation of somatic stem cells in vivo
Meacham, C. E., DeVilbiss, A. W., & Morrison, S. J. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00462-1 · Cited by 85
Metadata
- Authors
- Liang, R., Arif, T., Kalmykova, S., Kasianov, A., Lin, M., Menon, V., Qiu, J., Bernitz, J. M., Moore, K., Lin, F., Benson, D. L., Tzavaras, N., Mahajan, M., Papatsenko, D., & Ghaffari, S.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 26
- Issue
- 3
- Pages
- 359-376.e7
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W3007233540
- Cited by
- 254
- References
- 27
- FWCI
- 20.12
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Liang, R., Arif, T., Kalmykova, S., Kasianov, A., Lin, M., Menon, V., Qiu, J., Bernitz, J. M., Moore, K., Lin, F., Benson, D. L., Tzavaras, N., Mahajan, M., Papatsenko, D., & Ghaffari, S. (2020). Restraining Lysosomal Activity Preserves Hematopoietic Stem Cell Quiescence and Potency. Cell Stem Cell. https://doi.org/10.1016/j.stem.2020.01.013
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