Haematopoietic stem cell survival and transplantation efficacy is limited by the BH3-only proteins Bim and Bmf

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...

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Main Authors:	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
Format:	Online
Language:	English
Published:	WILEY-VCH Verlag 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3569658/

id	pubmed-3569658
recordtype	oai_dc
spelling	pubmed-35696582013-02-12 Haematopoietic stem cell survival and transplantation efficacy is limited by the BH3-only proteins Bim and Bmf 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 Research Articles 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. WILEY-VCH Verlag 2013-01 2012-11-24 /pmc/articles/PMC3569658/ /pubmed/23180554 http://dx.doi.org/10.1002/emmm.201201235 Text en Copyright © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	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
spellingShingle	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 Haematopoietic stem cell survival and transplantation efficacy is limited by the BH3-only proteins Bim and Bmf
author_facet	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
author_sort	Labi, Verena
title	Haematopoietic stem cell survival and transplantation efficacy is limited by the BH3-only proteins Bim and Bmf
title_short	Haematopoietic stem cell survival and transplantation efficacy is limited by the BH3-only proteins Bim and Bmf
title_full	Haematopoietic stem cell survival and transplantation efficacy is limited by the BH3-only proteins Bim and Bmf
title_fullStr	Haematopoietic stem cell survival and transplantation efficacy is limited by the BH3-only proteins Bim and Bmf
title_full_unstemmed	Haematopoietic stem cell survival and transplantation efficacy is limited by the BH3-only proteins Bim and Bmf
title_sort	haematopoietic stem cell survival and transplantation efficacy is limited by the bh3-only proteins bim and bmf
description	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.
publisher	WILEY-VCH Verlag
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3569658/
_version_	1611954017181630464

Haematopoietic stem cell survival and transplantation efficacy is limited by the BH3-only proteins Bim and Bmf

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