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  • Title: Reprogramming of chimpanzee fibroblasts into a multipotent cancerous but not fully pluripotent state by transducing iPSC factors in 2i/LIF culture.
    Author: Lin ZY, Nakai R, Hirai H, Kozuka D, Katayama S, Nakamura SI, Okada S, Kitajima R, Imai H, Okano H, Imamura M.
    Journal: Differentiation; 2020; 112():67-76. PubMed ID: 32045848.
    Abstract:
    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.
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