Generation of integration-free and region-specific neural progenitors from primate fibroblasts

Cell Rep. 2013 May 30;3(5):1580-91. doi: 10.1016/j.celrep.2013.04.004. Epub 2013 May 2.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzamides / pharmacology
  • Cell Differentiation
  • Dioxoles / pharmacology
  • Fibroblasts / cytology*
  • Fibroblasts / drug effects
  • Haplorhini
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / transplantation
  • Leukemia Inhibitory Factor / pharmacology
  • Neural Stem Cells / cytology*
  • Neuroglia / cytology
  • Neuroglia / metabolism
  • Neurons / cytology
  • Neurons / metabolism
  • Prosencephalon / metabolism
  • Pyridines / pharmacology
  • Pyrimidines / pharmacology
  • Rhombencephalon / metabolism
  • Temperature


  • 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide
  • Benzamides
  • Chir 99021
  • Dioxoles
  • Leukemia Inhibitory Factor
  • Pyridines
  • Pyrimidines