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Haematopoietic stem cell survival and transplantation efficacy is limited by the BH3-only proteins Bim and Bmf.
- Source :
- EMBO Molecular Medicine; Jan2013, Vol. 5 Issue 1, p122-136, 15p
- Publication Year :
- 2013
-
Abstract
- Anti-apoptotic Bcl-2 family members are critical for the regulation of haematopoietic stem and progenitor cell (HSPC) survival. Little is known about the role of their pro-apoptotic antagonists, i.e. 'BH3-only' proteins, in this cell compartment. Based on the analysis of cytokine deprivation-induced changes in mRNA expression levels of Bcl-2 family proteins, we determined the consequences of BH3-only protein depletion on HSPC survival in culture and, for selected candidates, on engraftment in vivo. Thereby, we revealed a critical role for Bim and Bmf as regulators of HSPC dynamics both during early engraftment and long-term reconstitution. HSPCs derived from wild-type donors were readily displaced by Bim- or Bmf-deficient or Bcl-2-overexpressing HSPCs as early as 10 days after engraftment. Moreover, in the absence of Bim, significantly lower numbers of transplanted HSPCs were able to fully engraft radio-depleted recipients. Finally, we provide proof of principle that RNAi-based reduction of BIM or BMF, or overexpression of BCL-2 in human CD34<superscript>+</superscript> cord blood cells may be an attractive therapeutic option to increase stem cell survival and transplantation efficacy. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 17574676
- Volume :
- 5
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- EMBO Molecular Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 84577751
- Full Text :
- https://doi.org/10.1002/emmm.201201235