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

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 serin...

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Detalles Bibliográficos
Autores principales: Karatepe, Kutay, Zhu, Haiyan, Zhang, Xiaoyu, Guo, Rongxia, Kambara, Hiroto, Loison, Fabien, Liu, Peng, Yu, Hongbo, Ren, Qian, Luo, Xiao, Manis, John, Cheng, Tao, Ma, Fengxia, Xu, Yuanfu, Luo, Hongbo R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235012/
https://www.ncbi.nlm.nih.gov/pubmed/30392974
http://dx.doi.org/10.1016/j.stemcr.2018.10.004
Descripción
Sumario: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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