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

doi:10.1038/s41536-021-00199-z

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 journal › Article › peer-review

11 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 language	English
Article number	4
Journal	npj Regenerative Medicine
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41536-021-00199-z
Publication status	Published - 2022 Dec

Bibliographical note

Funding Information:
We thank Dr. Gabsang Lee (Johns Hopkins University, Baltimore, USA) for providing the SOX10::eGFP reporter hESCs. This work was supported by the Bio & Medical Technology Development Program of the National Research Foundation of Korea, funded by the Korea Ministry of Science, ICT, & Future Planning (MSIP) project no. NRF-2015M3A9B4071074, a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI18C2166), and the School of Life Sciences and Biotechnology for BK21 PLUS, Korea University, and STEMLAB, INC.

Publisher Copyright:
© 2022, The Author(s).

ASJC Scopus subject areas

Medicine (miscellaneous)
Biomedical Engineering
Developmental Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41536-021-00199-z

Cite this

Yun, W., Choi, K. A., Hwang, I., Zheng, J., Park, M., Hong, W., Jang, A. Y., Kim, J. H., Choi, W., Kim, D. S., Kim, I. Y., Kim, Y. J., Liu, Y., Yoon, B. S., Park, G., Song, G., Hong, S., & You, S. (2022). OCT4-induced oligodendrocyte progenitor cells promote remyelination and ameliorate disease. npj Regenerative Medicine, 7(1), Article 4. https://doi.org/10.1038/s41536-021-00199-z

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title = "OCT4-induced oligodendrocyte progenitor cells promote remyelination and ameliorate disease",

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.",

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

note = "Funding Information: We thank Dr. Gabsang Lee (Johns Hopkins University, Baltimore, USA) for providing the SOX10::eGFP reporter hESCs. This work was supported by the Bio & Medical Technology Development Program of the National Research Foundation of Korea, funded by the Korea Ministry of Science, ICT, & Future Planning (MSIP) project no. NRF-2015M3A9B4071074, a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI18C2166), and the School of Life Sciences and Biotechnology for BK21 PLUS, Korea University, and STEMLAB, INC. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

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AU - Yun, Wonjin

AU - Choi, Kyung Ah

AU - Hwang, Insik

AU - Zheng, Jie

AU - Park, Minji

AU - Hong, Wonjun

AU - Jang, Ah Young

AU - Kim, Jeong Hee

AU - Choi, Wonji

AU - Kim, Dae Sung

AU - Kim, In Yong

AU - Kim, Yong Jun

AU - Liu, Ying

AU - Yoon, Byung Sun

AU - Park, Gyuman

AU - Song, Gwonhwa

AU - Hong, Sunghoi

AU - You, Seungkwon

N1 - Funding Information: We thank Dr. Gabsang Lee (Johns Hopkins University, Baltimore, USA) for providing the SOX10::eGFP reporter hESCs. This work was supported by the Bio & Medical Technology Development Program of the National Research Foundation of Korea, funded by the Korea Ministry of Science, ICT, & Future Planning (MSIP) project no. NRF-2015M3A9B4071074, a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI18C2166), and the School of Life Sciences and Biotechnology for BK21 PLUS, Korea University, and STEMLAB, INC. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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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DO - 10.1038/s41536-021-00199-z

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ER -

OCT4-induced oligodendrocyte progenitor cells promote remyelination and ameliorate disease

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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