OCT4-induced oligodendrocyte progenitor cells promote remyelination and ameliorate disease

Wonjin Yun, Kyung Ah Choi, Insik Hwang, Jie Zheng, Minji Park, Wonjun Hong, Ah Young Jang, Jeong Hee Kim, Wonji Choi, Dae Sung Kim, In Yong Kim, Yong Jun Kim, Ying Liu, Byung Sun Yoon, Gyuman Park, Gwonhwa Song, Sunghoi Hong, Seungkwon You

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

The generation of human oligodendrocyte progenitor cells (OPCs) may be therapeutically valuable for human demyelinating diseases such as multiple sclerosis. Here, we report the direct reprogramming of human somatic cells into expandable induced OPCs (iOPCs) using a combination of OCT4 and a small molecule cocktail. This method enables generation of A2B5+ (an early marker for OPCs) iOPCs within 2 weeks retaining the ability to differentiate into MBP-positive mature oligodendrocytes. RNA-seq analysis revealed that the transcriptome of O4+ iOPCs was similar to that of O4+ OPCs and ChIP-seq analysis revealed that putative OCT4-binding regions were detected in the regulatory elements of CNS development-related genes. Notably, engrafted iOPCs remyelinated the brains of adult shiverer mice and experimental autoimmune encephalomyelitis mice with MOG-induced 14 weeks after transplantation. In conclusion, our study may contribute to the development of therapeutic approaches for neurological disorders, as well as facilitate the understanding of the molecular mechanisms underlying glial development.

Original languageEnglish
Article number4
Journalnpj Regenerative Medicine
Volume7
Issue number1
DOIs
Publication statusPublished - 2022 Dec

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Developmental Biology
  • Cell Biology

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