C/EBPα bypasses cell cycle-dependency during immune cell transdifferentiation.
Cell Cycle
; 11(14): 2739-46, 2012 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-22771961
ABSTRACT
Our earlier work has shown that pre-B cells can be converted into macrophage-like cells by overexpression of the transcription factor C/EBPα or C/EBPß with high efficiency. Using inducible pre-B cell lines, we have now investigated the role of cell division during C/EBP-induced reprogramming. The majority of cells reprogrammed by C/EBPα incorporated BrdU before arresting at G(0), and all C/EBPß-induced cells incorporated the compound. This contrasts with reports from other systems where transdifferentiating cells essentially do not divide. Although inhibition of DNA synthesis led to an impairment of C/EBPα-induced transdifferentiation, sorted G(0)/G(1) and G(2)/M fractions showed no significant differences in their reprogramming kinetics. In addition, knocking-down p53 did not accelerate the transdifferentiation frequency, as it has been described for reprogramming of induced pluripotent (iPS) cells. Time-lapse experiments showed that, after C/EBPα induction, approximately 90% of cells divide once or twice, while 8% do not divide at all before acquiring a macrophage phenotype, supporting our BrdU incorporation results. Importantly, the non-dividing cell subset expressed the highest levels of C/EBPα and was the fastest in differentiating, suggesting that high levels of C/EBPα accelerate both the switching process and the cells' growth arrest. Our data show that traversing the cell cycle is not strictly required for pre-B cell to macrophage conversion and provides new evidence for the notion that the mechanisms of transcription factor induced transdifferentiation and iPS cell reprogramming differ.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Proteína alfa Estimuladora de Ligação a CCAAT
/
Transdiferenciação Celular
Limite:
Animals
Idioma:
En
Revista:
Cell Cycle
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Espanha