Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 79, Issue 4, Pages -Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-022-04200-w
Keywords
Mitochondrial metabolism; Autophagy; Akt-mTOR; p38MAPK; Cell niche; Extracellular matrix
Categories
Funding
- National Key R&D Program of China [2017YFA0106700]
- National Science Foundation of China [82170115]
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Hematopoietic stem cells (HSCs) remain dormant in a cell-cycle quiescence state to maintain their self-renewal capacity and play a crucial role in hematopoietic system homeostasis. Dysregulation of quiescence can lead to HSC dysfunction and result in abnormal hematopoiesis and leukemia transformation. Intrinsic molecular networks and extrinsic signals regulate HSC quiescence, and cell metabolism drives the transition between quiescence and activation of HSCs. Investigating the complex regulatory networks of HSC quiescence expands our understanding of blood cell formation and has clinical implications.
Hematopoietic stem cells (HSCs) are primarily dormant in a cell-cycle quiescence state to preserve their self-renewal capacity and long-term maintenance, which is essential for the homeostasis of hematopoietic system. Dysregulation of quiescence causes HSC dysfunction and may result in aberrant hematopoiesis (e.g., myelodysplastic syndrome and bone marrow failure syndromes) and leukemia transformation. Accumulating evidence indicates that both intrinsic molecular networks and extrinsic signals regulate HSC quiescence, including cell-cycle regulators, transcription factors, epigenetic factors, and niche factors. Further, the transition between quiescence and activation of HSCs is a continuous developmental path driven by cell metabolism (e.g., protein synthesis, glycolysis, oxidative phosphorylation, and autophagy). Elucidating the complex regulatory networks of HSC quiescence will expand the knowledge of HSC hemostasis and benefit for clinical HSC use. Here, we review the current understanding and progression on the molecular and metabolic regulation of HSC quiescence, providing a more complete picture regarding the mechanisms of HSC quiescence maintenance.
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