Journal
STEM CELL REPORTS
Volume 11, Issue 5, Pages 1092-1105Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2018.10.004
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Funding
- Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2018RC31002, 2017PT31033]
- Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences [2017-I2M-1-015]
- State Key Laboratory of Experimental Hematology Research Grant [157-Z18-01]
- National Basic Research Program of China [2015CB964903, 2012CB966403]
- National Natural Science Foundation of China [31271484, 31471116]
- Natural Science Foundation of Tianjin City [12JCZDJC24600]
- NIH [R01AI103142, R01HL092020, P01 HL095489]
- FAMRI [CIA 123008]
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Hematopoietic stem and progenitor cells (HSPCs) undergo self-renewal and differentiation to guarantee a constant supply of short-lived blood cells. Both intrinsic and extrinsic factors determine HSPC fate, but the underlying mechanisms remain elusive. Here, we report that Proteinase 3 (PR3), a serine protease mainly confined to granulocytes, is also expressed in HSPCs. PR3 deficiency intrinsically suppressed cleavage and activation of caspase-3, leading to expansion of the bone marrow (BM) HSPC population due to decreased apoptosis. PR3-deficient HSPCs outcompete the long-term reconstitution potential of wild-type counterparts. Collectively, our results establish PR3 as a physiological regulator of HSPC numbers. PR3 inhibition is a potential therapeutic target to accelerate and increase the efficiency of BM reconstitution during transplantation.
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