한빛사논문
Wonjin Yun1,2,10, Kyung-Ah Choi3,10, Insik Hwang3, Jie Zheng1,2, Minji Park1, Wonjun Hong1,2, Ah-Young Jang3, Jeong Hee Kim4, Wonji Choi1,2, Dae-Sung Kim2,5, In Yong Kim1,2, Yong Jun Kim4,6, Ying Liu7, Byung Sun Yoon8, Gyuman Park8, Gwonhwa Song1,2, Sunghoi Hong3,9,* and Seungkwon You1,2,*
1Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea. 2Institute of Animal Molecular Biotechnology, Korea University, Seoul 136-701, Republic of Korea. 3School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul, Republic of Korea. 4Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea. 5Laboratory of Reprogramming & Differentiation, Department of Biotechnology, College of Life Science and Biotechnology, Korea University, Seoul 136-701, Republic of Korea. 6Department of Pathology, College of Medicine, Kyung Hee University, Seoul, Republic of Korea. 7Department of Neurosurgery, the University of Texas Health Science Center at Houston, Houston, TX, USA. 8Institute of Regenerative Medicine, STEMLAB, Inc., Seoul 02841, Republic of Korea. 9Department of Integrated Biomedical and Life Science, College of Health Science, Korea University, Seoul, Republic of Korea. 10These authors contributed equally: Wonjin Yun, Kyung-Ah Choi.
*Corresponding author.
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.
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