Journal
NPJ REGENERATIVE MEDICINE
Volume 7, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41536-021-00199-z
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Funding
- Bio & Medical Technology Development Program of the National Research Foundation of Korea - Korea Ministry of Science, ICT, & Future Planning (MSIP) [NRF-2015M3A9B4071074]
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI18C2166]
- School of Life Sciences and Biotechnology for BK21 PLUS, Korea University
- STEMLAB, INC.
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This study successfully reprogrammed human somatic cells into expandable induced OPCs (iOPCs) using OCT4 and a small molecule cocktail. The generated iOPCs are capable of differentiating into mature oligodendrocytes and have the potential to remyelinate damaged brains. This research has significant implications for the development of therapeutic approaches for neurological disorders.
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.
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