Rapid and efficient generation of oligodendrocytes from human induced pluripotent stem cells using transcription factors

Proc Natl Acad Sci U S A. 2017 Mar 14;114(11):E2243-E2252. doi: 10.1073/pnas.1614412114. Epub 2017 Feb 28.

Abstract

Rapid and efficient protocols to generate oligodendrocytes (OL) from human induced pluripotent stem cells (iPSC) are currently lacking, but may be a key technology to understand the biology of myelin diseases and to develop treatments for such disorders. Here, we demonstrate that the induction of three transcription factors (SOX10, OLIG2, NKX6.2) in iPSC-derived neural progenitor cells is sufficient to rapidly generate O4+ OL with an efficiency of up to 70% in 28 d and a global gene-expression profile comparable to primary human OL. We further demonstrate that iPSC-derived OL disperse and myelinate the CNS of Mbpshi/shiRag-/- mice during development and after demyelination, are suitable for in vitro myelination assays, disease modeling, and screening of pharmacological compounds potentially promoting oligodendroglial differentiation. Thus, the strategy presented here to generate OL from iPSC may facilitate the studying of human myelin diseases and the development of high-throughput screening platforms for drug discovery.

Keywords: disease modeling; forward patterning; human iPSC; myelination; oligodendrocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Brain / metabolism
  • Brain / pathology
  • Brain / ultrastructure
  • Cell Death / genetics
  • Cell Differentiation / genetics*
  • Cell Lineage / genetics
  • Cells, Cultured
  • Cluster Analysis
  • Demyelinating Diseases / genetics
  • Demyelinating Diseases / metabolism
  • Demyelinating Diseases / pathology
  • Disease Models, Animal
  • Ectopic Gene Expression
  • Gene Expression Profiling
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism*
  • Mice
  • Mutation
  • Myelin Basic Protein / genetics
  • Myelin Basic Protein / metabolism
  • Myelin Sheath / genetics
  • Myelin Sheath / metabolism
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Oligodendroglia / cytology*
  • Oligodendroglia / metabolism*
  • Oxidative Stress
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Spinal Cord / ultrastructure
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcriptome
  • tau Proteins / genetics
  • tau Proteins / metabolism

Substances

  • Biomarkers
  • Myelin Basic Protein
  • Transcription Factors
  • tau Proteins