One-step Reprogramming of Human Fibroblasts into Oligodendrocyte-like Cells by SOX10, OLIG2, and NKX6.2

Stem Cell Reports. 2021 Apr 13;16(4):771-783. doi: 10.1016/j.stemcr.2021.03.001. Epub 2021 Mar 25.


Limited access to human oligodendrocytes impairs better understanding of oligodendrocyte pathology in myelin diseases. Here, we describe a method to robustly convert human fibroblasts directly into oligodendrocyte-like cells (dc-hiOLs), which allows evaluation of remyelination-promoting compounds and disease modeling. Ectopic expression of SOX10, OLIG2, and NKX6.2 in human fibroblasts results in rapid generation of O4+ cells, which further differentiate into MBP+ mature oligodendrocyte-like cells within 16 days. dc-hiOLs undergo chromatin remodeling to express oligodendrocyte markers, ensheath axons, and nanofibers in vitro, respond to promyelination compound treatment, and recapitulate in vitro oligodendroglial pathologies associated with Pelizaeus-Merzbacher leukodystrophy related to PLP1 mutations. Furthermore, DNA methylome analysis provides evidence that the CpG methylation pattern significantly differs between dc-hiOLs derived from fibroblasts of young and old donors, indicating the maintenance of the source cells' "age." In summary, dc-hiOLs represent a reproducible technology that could contribute to personalized medicine in the field of myelin diseases.

Keywords: ATAC-seq; PMD; compound screenin; direct conversion; epigenetic age; human fibroblasts; oligodendrocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Cell Line
  • Cell Movement
  • Cellular Reprogramming*
  • Chromatin / metabolism
  • Chromatin Assembly and Disassembly
  • Epigenesis, Genetic
  • Fibroblasts / cytology*
  • Fibroblasts / metabolism*
  • Gene Silencing
  • Homeodomain Proteins / metabolism*
  • Humans
  • Myelin Sheath / metabolism
  • Oligodendrocyte Transcription Factor 2 / metabolism*
  • Oligodendroglia / cytology*
  • Oligodendroglia / metabolism*
  • Pelizaeus-Merzbacher Disease / genetics
  • Pelizaeus-Merzbacher Disease / pathology
  • SOXE Transcription Factors / metabolism*
  • Transcription, Genetic
  • Transgenes


  • Chromatin
  • Homeodomain Proteins
  • NKX6-2 protein, human
  • OLIG2 protein, human
  • Oligodendrocyte Transcription Factor 2
  • SOX10 protein, human
  • SOXE Transcription Factors