SOX10 Single Transcription Factor-Based Fast and Efficient Generation of Oligodendrocytes from Human Pluripotent Stem Cells

Stem Cell Reports. 2018 Feb 13;10(2):655-672. doi: 10.1016/j.stemcr.2017.12.014. Epub 2018 Jan 11.


Scarce access to primary samples and lack of efficient protocols to generate oligodendrocytes (OLs) from human pluripotent stem cells (hPSCs) are hampering our understanding of OL biology and the development of novel therapies. Here, we demonstrate that overexpression of the transcription factor SOX10 is sufficient to generate surface antigen O4-positive (O4+) and myelin basic protein-positive OLs from hPSCs in only 22 days, including from patients with multiple sclerosis or amyotrophic lateral sclerosis. The SOX10-induced O4+ population resembles primary human OLs at the transcriptome level and can myelinate neurons in vivo. Using in vitro OL-neuron co-cultures, myelination of neurons by OLs can also be demonstrated, which can be adapted to a high-throughput screening format to test the response of pro-myelinating drugs. In conclusion, we provide an approach to generate OLs in a very rapid and efficient manner, which can be used for disease modeling, drug discovery efforts, and potentially for therapeutic OL transplantation.

Keywords: amyotrophic lateral sclerosis; disease modeling; drug screening; induced pluripotent stem cells (iPSCs); multiple sclerosis; myelination; oligodendrocyte.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / therapy
  • Antigens, Surface / genetics
  • Cell Differentiation / genetics*
  • Gene Expression Regulation, Developmental
  • Humans
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / pathology
  • Multiple Sclerosis / therapy
  • Myelin Basic Protein / genetics
  • Neurons / pathology
  • Neurons / transplantation
  • Oligodendroglia / cytology
  • Oligodendroglia / metabolism*
  • Oligodendroglia / transplantation
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism*
  • Pluripotent Stem Cells / transplantation
  • SOXE Transcription Factors / genetics*
  • Transcriptome / genetics


  • Antigens, Surface
  • Myelin Basic Protein
  • SOX10 protein, human
  • SOXE Transcription Factors