title: Rapid and efficient reprogramming of somatic cells to induced pluripotent stem cells by retinoic acid receptor gamma and liver receptor homolog 1.
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.
authors: Wellcome Trust Sanger Institute, Hinxton CB10 1HH,  United Kingdom.
authors: Wei
authors: W
authors: Wang
authors: Jian
authors: J
authors: Yang
authors: Hui
authors: H
authors: Liu
authors: Dong
authors: D
authors: Lu
authors: Xiongfeng
authors: X
authors: Chen
authors: Zenon
authors: Z
authors: Zenonos
authors: Lia S
authors: LS
authors: Campos
authors: Roland
authors: R
authors: Rad
authors: Ge
authors: G
authors: Guo
authors: Shujun
authors: S
authors: Zhang
authors: Allan
authors: A
authors: Bradley
authors: Pentao
authors: P
authors: Liu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D018168:Receptors, Retinoic Acid / Q000502:physiology*; D015398:Signal Transduction; D000097768:Retinoic Acid Receptor gamma
chemical_list: D000090062:Kruppel-Like Factor 4; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D000097768:Retinoic Acid Receptor gamma; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; C082631:NR5A2 protein, human; C431936:Nr5a2 protein, mouse