MafB/c-Maf deficiency enables self-renewal of differentiated functional macrophages.
Science
; 326(5954): 867-71, 2009 Nov 06.
Article
em En
| MEDLINE
| ID: mdl-19892988
ABSTRACT
In metazoan organisms, terminal differentiation is generally tightly linked to cell cycle exit, whereas the undifferentiated state of pluripotent stem cells is associated with unlimited self-renewal. Here, we report that combined deficiency for the transcription factors MafB and c-Maf enables extended expansion of mature monocytes and macrophages in culture without loss of differentiated phenotype and function. Upon transplantation, the expanded cells are nontumorigenic and contribute to functional macrophage populations in vivo. Small hairpin RNA inactivation shows that continuous proliferation of MafB/c-Maf deficient macrophages requires concomitant up-regulation of two pluripotent stem cell-inducing factors, KLF4 and c-Myc. Our results indicate that MafB/c-MafB deficiency renders self-renewal compatible with terminal differentiation. It thus appears possible to amplify functional differentiated cells without malignant transformation or stem cell intermediates.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proliferação de Células
/
Fator de Transcrição MafB
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Proteínas Proto-Oncogênicas c-maf
/
Macrófagos
Limite:
Animals
Idioma:
En
Revista:
Science
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
França