The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Metabolic Regulation by the Mitochondrial Phosphatase PTPMT1 Is Required for Hematopoietic Stem Cell Differentiation
Open accessAbstract
SUMMARY The regulation and coordination of mitochondrial metabolism with hematopoietic stem cell (HSC) self-renewal and differentiation is not fully understood. Here we report that depletion of PTPMT1, a PTEN-like mitochondrial phosphatase, in inducible or hematopoietic-cell-specific knockout mice resulted in hematopoietic failure due to changes in the cell cycle and a block in the differentiation of HSCs. Surprisingly, the HSC pool was increased by ~40-fold in PTPMT1 knockout mice. Reintroduction of wild-type PTPMT1, but not catalytically deficient PTPMT1 or truncated PTPMT1 lacking mitochondrial localization, restored differentiation capabilities of PTPMT1 knockout HSCs. Further analyses demonstrated that PTPMT1 deficiency altered mitochondrial metabolism and that phosphatidylinositol phosphate substrates of PTPMT1 directly enhanced fatty-acid-induced activation of mitochondrial uncoupling protein 2. Intriguingly, depletion of PTPMT1 from myeloid, T lymphoid, or B lymphoid progenitors did not cause any defects in lineage-specific knockout mice. This study establishes a crucial role of PTPMT1 in the metabolic regulation of HSC function.
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Cites
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Self-citationp57 is required for quiescence and maintenance of adult hematopoietic stem cells
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Cited by
Metabolic requirements for the maintenance of self-renewing stem cells
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A single-cell resolution map of mouse hematopoietic stem and progenitor cell differentiation
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Metadata
- Authors
- Yu, W.-M., Liu, X., Shen, J., Jovanovic, O., Pohl, E. E., Gerson, S. L., Finkel, T., Broxmeyer, H. E., & Qu, C.-K.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 12
- Issue
- 1
- Pages
- 62-74
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W1987761030
- Cited by
- 341
- References
- 12
- FWCI
- 17.06
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Yu, W.-M., Liu, X., Shen, J., Jovanovic, O., Pohl, E. E., Gerson, S. L., Finkel, T., Broxmeyer, H. E., & Qu, C.-K. (2013). Metabolic Regulation by the Mitochondrial Phosphatase PTPMT1 Is Required for Hematopoietic Stem Cell Differentiation. Cell Stem Cell. https://doi.org/10.1016/j.stem.2012.11.022
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