These authors contributed equally to this work.
Haematopoietic stem cell survival and transplantation efficacy is limited by the BH3-only proteins Bim and Bmf
Article first published online: 24 NOV 2012
Copyright © 2013 EMBO Molecular Medicine
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
EMBO Molecular Medicine
Volume 5, Issue 1, pages 122–136, January 2013
How to Cite
Labi, V., Bertele, D., Woess, C., Tischner, D., Bock, F. J., Schwemmers, S., Pahl, H. L., Geley, S., Kunze, M., Niemeyer, C. M., Villunger, A. and Erlacher, M. (2013), Haematopoietic stem cell survival and transplantation efficacy is limited by the BH3-only proteins Bim and Bmf. EMBO Mol Med, 5: 122–136. doi: 10.1002/emmm.201201235
- Issue published online: 3 JAN 2013
- Article first published online: 24 NOV 2012
- Accepted manuscript online: 15 OCT 2012 05:20AM EST
- Manuscript Accepted: 8 OCT 2012
- Manuscript Revised: 5 OCT 2012
- Manuscript Received: 25 JAN 2012
- Funded Access
- Bcl-2 protein family;
- haematopoietic stem cell transplantation
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+ cord blood cells may be an attractive therapeutic option to increase stem cell survival and transplantation efficacy.