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Proteinase 3 Limits the Number of Hematopoietic Stem and Progenitor Cells in Murine Bone Marrow

Kutay Karatepe1, Haiyan Zhu2, Xiaoyu Zhang1

  • 1Department of Lab Medicine, The Stem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pathology, Harvard Medical School, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.

Stem Cell Reports
|November 6, 2018
PubMed

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.

Keywords:
Proteinase 3apoptosishematopoiesishematopoietic progenitor cellhematopoietic stem cell

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