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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.
Afiliação
  • Labi V; Division of Developmental Immunology, Biocenter, Innsbruck Medical University, Innsbruck, Austria. verena.labi@mdc-berlin.de
EMBO Mol Med ; 5(1): 122-36, 2013 01.
Article em En | MEDLINE | ID: mdl-23180554
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Hematopoéticas / Proteínas Proto-Oncogênicas / Transplante de Células-Tronco Hematopoéticas / Proteínas Adaptadoras de Transdução de Sinal / Proteínas Reguladoras de Apoptose / Proteínas de Membrana Limite: Animals / Humans Idioma: En Ano de publicação: 2013 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Hematopoéticas / Proteínas Proto-Oncogênicas / Transplante de Células-Tronco Hematopoéticas / Proteínas Adaptadoras de Transdução de Sinal / Proteínas Reguladoras de Apoptose / Proteínas de Membrana Limite: Animals / Humans Idioma: En Ano de publicação: 2013 Tipo de documento: Article