Rapid and efficient reprogramming of somatic cells to induced pluripotent stem cells by retinoic acid receptor gamma and liver receptor homolog 1.
Proc Natl Acad Sci U S A
; 108(45): 18283-8, 2011 Nov 08.
Article
em En
| MEDLINE
| ID: mdl-21990348
ABSTRACT
Somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) by expressing four transcription factors Oct4, Sox2, Klf4, and c-Myc. Here we report that enhancing RA signaling by expressing RA receptors (RARs) or by RA agonists profoundly promoted reprogramming, but inhibiting it using a RAR-α dominant-negative form completely blocked it. Coexpressing Rarg (RAR-γ) and Lrh-1 (liver receptor homologue 1; Nr5a2) with the four factors greatly accelerated reprogramming so that reprogramming of mouse embryonic fibroblast cells to ground-state iPSCs requires only 4 d induction of these six factors. The six-factor combination readily reprogrammed primary human neonatal and adult fibroblast cells to exogenous factor-independent iPSCs, which resembled ground-state mouse ES cells in growth properties, gene expression, and signaling dependency. Our findings demonstrate that signaling through RARs has critical roles in molecular reprogramming and that the synergistic interaction between Rarg and Lrh1 directs reprogramming toward ground-state pluripotency. The human iPSCs described here should facilitate functional analysis of the human genome.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
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Receptores do Ácido Retinoico
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Receptores Citoplasmáticos e Nucleares
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Células-Tronco Pluripotentes
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article