| First Author | Karatepe K | Year | 2018 |
| Journal | Stem Cell Reports | Volume | 11 |
| Issue | 5 | Pages | 1092-1105 |
| PubMed ID | 30392974 | Mgi Jnum | J:310680 |
| Mgi Id | MGI:6763718 | Doi | 10.1016/j.stemcr.2018.10.004 |
| Citation | Karatepe K, et al. (2018) Proteinase 3 Limits the Number of Hematopoietic Stem and Progenitor Cells in Murine Bone Marrow. Stem Cell Reports 11(5):1092-1105 |
| abstractText | 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. |
