Abstract
The stringent regulation of hematopoietic stem cell (HSC) quiescence versus cell cycle progression is essential for the preservation of a pool of long-term self-renewing cells and vital for sustaining an adequate supply of all blood lineages throughout life. Cell growth, the process that is mass increase, serves as a trigger for cell cycle progression and is regulated predominantly by mammalian target of rapamycin complex 1 (mTORC1) signaling. Emerging data from various mice models show deletion of several mTORC1 negative regulators, including PTEN, TSC1, PML and Fbxw7 result in similar HSC phenotypes characterized as HSC hyper-proliferation and subsequent exhaustion, and defective repopulating potential. Further pharmacological approaches show that PTEN, TSC1 and PML regulate HSC maintenance through mTORC1. mTORC1-mediated cell growth regulatory circuits thus play a critical role in the regulation of HSC quiescence.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Proliferation
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F-Box Proteins / metabolism*
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F-Box-WD Repeat-Containing Protein 7
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Hematopoietic Stem Cells / metabolism
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Hematopoietic Stem Cells / physiology*
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Mice
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Nuclear Proteins / metabolism*
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PTEN Phosphohydrolase / metabolism*
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Promyelocytic Leukemia Protein
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Signal Transduction / physiology
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription Factors / physiology*
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Tuberous Sclerosis Complex 1 Protein
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Tumor Suppressor Proteins / metabolism*
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Ubiquitin-Protein Ligases / metabolism*
Substances
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Crtc1 protein, mouse
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F-Box Proteins
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F-Box-WD Repeat-Containing Protein 7
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Fbxw7 protein, mouse
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Nuclear Proteins
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Pml protein, mouse
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Promyelocytic Leukemia Protein
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Transcription Factors
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Tsc1 protein, mouse
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Tuberous Sclerosis Complex 1 Protein
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Tumor Suppressor Proteins
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Ubiquitin-Protein Ligases
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PTEN Phosphohydrolase
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Pten protein, mouse