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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)67-76
Number of pages10
JournalDifferentiation
Volume112
DOIs
Publication statusPublished - 2020 Mar 1

Keywords

  • Chimpanzee
  • Pluripotency
  • Reprogramming
  • iPSC

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology
  • Cancer Research

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    Lin, Z. Y. C., Nakai, R., Hirai, H., Kozuka, D., Katayama, S., Nakamura, S. I., Okada, S., Kitajima, R., Imai, H., Okano, H., & Imamura, M. (2020). Reprogramming of chimpanzee fibroblasts into a multipotent cancerous but not fully pluripotent state by transducing iPSC factors in 2i/LIF culture. Differentiation, 112, 67-76. https://doi.org/10.1016/j.diff.2020.01.002