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1.
Differentiation ; 112: 67-76, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32045848

RESUMO

To induce and maintain naïve pluripotency in mouse embryonic and induced pluripotent stem cells (ESCs/iPSCs), chemically defined N2B27 medium with PD0325901, CHIR99021, and leukemia inhibitory factor (2i/LIF) is a classic and simple condition. However, this method cannot be simply extrapolated to human ESCs/iPSCs that are principally stabilized in primed pluripotency and become primitive neuroepithelium-like cells in N2B27+2i/LIF culture. Here, we assessed iPSC reprogramming of fibroblasts from chimpanzee, our closest living relative, in N2B27+2i/LIF culture. Under this condition, chimpanzee cells formed alkaline phosphatase-positive dome-shaped colonies. The colony-forming cells could be stably expanded by serial passaging without a ROCK inhibitor. However, their gene expression was distinct from iPSCs and neuroepithelium. They expressed the OCT3/4 transgene and a subset of transcripts associated with pluripotency, mesenchymal-epithelial transition, and neural crest formation. These cells exhibited a differentiation potential into the three germ layers in vivo and in vitro. The current study demonstrated that iPSC reprogramming in N2B27+2i/LIF culture converted chimpanzee fibroblasts into a multipotent cancerous state with unique gene expression, but not fully pluripotent stem cells.


Assuntos
Diferenciação Celular/genética , Reprogramação Celular/genética , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Multipotentes/citologia , Animais , Benzamidas/farmacologia , Diferenciação Celular/efeitos dos fármacos , Reprogramação Celular/efeitos dos fármacos , Difenilamina/análogos & derivados , Difenilamina/farmacologia , Transição Epitelial-Mesenquimal/genética , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Camadas Germinativas/efeitos dos fármacos , Camadas Germinativas/crescimento & desenvolvimento , Humanos , Fator Inibidor de Leucemia/farmacologia , Camundongos , Células-Tronco Multipotentes/efeitos dos fármacos , Crista Neural/citologia , Pan troglodytes , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/efeitos dos fármacos , Piridinas/farmacologia , Pirimidinas/farmacologia
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