Reprogramming of chimpanzee fibroblasts into a multipotent cancerous but not fully pluripotent state by transducing iPSC factors in 2i/LIF culture

Zachary Yu Ching Lin, Risako Nakai, Hirohisa Hirai, Daiki Kozuka, Seiya Katayama, Shin ichiro Nakamura, Sawako Okada, Ryunosuke Kitajima, Hiroo Imai, Hideyuki Okano, Masanori Imamura

研究成果: Article査読

1 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)67-76
ページ数10
ジャーナルDifferentiation
112
DOI
出版ステータスPublished - 2020 3 1

ASJC Scopus subject areas

  • 分子生物学
  • 発生生物学
  • 細胞生物学
  • 癌研究

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