Cell Reports (May 2013)

Generation of Integration-free and Region-Specific Neural Progenitors from Primate Fibroblasts

  • Jianfeng Lu,
  • Huisheng Liu,
  • Cindy Tzu-Ling Huang,
  • Hong Chen,
  • Zhongwei Du,
  • Yan Liu,
  • Mohammad Amin Sherafat,
  • Su-Chun Zhang

DOI
https://doi.org/10.1016/j.celrep.2013.04.004
Journal volume & issue
Vol. 3, no. 5
pp. 1580 – 1591

Abstract

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Postnatal and adult human and monkey fibroblasts were infected with Sendai virus containing the Yamanaka factors for 24 hr, then they were cultured in a chemically defined medium containing leukemia inhibitory factor (LIF), transforming growth factor (TGF)-β inhibitor SB431542, and glycogen synthase kinase (GSK)-3β inhibitor CHIR99021 at 39°C for inactivation of the virus. Induced neural progenitor (iNP) colonies appeared as early as day 13 and can be expanded for >20 passages. Under the same defined condition, no induced pluripotent stem cell (iPSC) colonies formed at either 37°C or 39°C. The iNPs predominantly express hindbrain genes and differentiate into hindbrain neurons, and when caudalized, they produced an enriched population of spinal motor neurons. Following transplantation into the forebrain, the iNP-derived cells retained the hindbrain identity. The ability to generate defined, integration-free iNPs from adult primate fibroblasts under a defined condition with predictable fate choices will facilitate disease modeling and therapeutic development.