Direct reprogramming of Sertoli cells into multipotent neural stem cells by defined factors

Cell Res. 2012 Jan;22(1):208-18. doi: 10.1038/cr.2011.175. Epub 2011 Nov 8.

Abstract

Multipotent neural stem/progenitor cells hold great promise for cell therapy. The reprogramming of fibroblasts to induced pluripotent stem cells as well as mature neurons suggests a possibility to convert a terminally differentiated somatic cell into a multipotent state without first establishing pluripotency. Here, we demonstrate that Sertoli cells derived from mesoderm can be directly converted into a multipotent state that possesses neural stem/progenitor cell properties. The induced neural stem/progenitor cells (iNSCs) express multiple NSC-specific markers, exhibit a global gene-expression profile similar to normal NSCs, and are capable of self-renewal and differentiating into glia and electrophysiologically functional neurons. iNSC-derived neurons stain positive for tyrosine hydroxylase (TH), γ-aminobutyric acid, and choline acetyltransferase. In addition, iNSCs can survive and generate synapses following transplantation into the dentate gyrus. Generation of iNSCs may have important implications for disease modeling and regenerative medicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / metabolism
  • Cell Differentiation
  • Cellular Reprogramming*
  • Choline O-Acetyltransferase / metabolism
  • Cloning, Molecular
  • Electrophysiological Phenomena
  • Fluorescent Antibody Technique
  • Gene Expression Profiling
  • Male
  • Mesoderm / cytology
  • Mesoderm / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Multipotent Stem Cells / cytology*
  • Multipotent Stem Cells / metabolism
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / transplantation
  • Neuroglia / cytology
  • Neuroglia / metabolism
  • Neurons / cytology
  • Neurons / metabolism
  • Retroviridae / genetics
  • Retroviridae / metabolism
  • Sertoli Cells / cytology*
  • Sertoli Cells / metabolism
  • Synapses / metabolism
  • Tyrosine 3-Monooxygenase / metabolism
  • gamma-Aminobutyric Acid / metabolism

Substances

  • gamma-Aminobutyric Acid
  • Tyrosine 3-Monooxygenase
  • Choline O-Acetyltransferase