Open AccessHaematopoietic stem cell survival and transplantation efficacy is limited by the BH3‐only proteins Bim and Bmf
Author(s) -
Labi Verena,
Bertele Daniela,
Woess Claudia,
Tischner Denise,
Bock Florian J.,
Schwemmers Sven,
Pahl Heike L.,
Geley Stephan,
Kunze Mirjam,
Niemeyer Charlotte M.,
Villunger Andreas,
Erlacher Miriam
Publication year - 2013
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201201235
Subject(s) - progenitor cell , haematopoiesis , stem cell , transplantation , biology , microbiology and biotechnology , cd34 , cord blood , cancer research , immunology , medicine
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.