한빛사 논문
Kee-Pyo Kim,1,2 Cui Li,3,12 Daria Bunina,4,8,12 Hyun-Woo Jeong,5 Julia Ghelman,6 Juyong Yoon,1 Borami Shin,1 Hongryeol Park,5 Dong Wook Han,7 Judith B. Zaugg,8 Johnny Kim,9 Tanja Kuhlmann,6 Ralf H. Adams,5 Kyung-Min Noh,4 Steven A. Goldman,3,10 and Hans R. Scholer1,11,13,*
1Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Munster 48149, Germany 2Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, 222 Banpo-daero Seocho-gu, Seoul 06591, Republic of Korea 3Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY 14642, USA
4Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg 69117, Germany
5Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Munster 48149, Germany 6Institute of Neuropathology, University Hospital Munster, Munster 48149, Germany 7School of Biotechnology and Healthcare, Wuyi University, Jiangmen 529020, China 8Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg 69117, Germany
9Department of Cardiac Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim 61231, Germany 10Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark 11Faculty of Medicine, University of Munster, Munster 48149, Germany
12These authors contributed equally
13Lead contact
*Corresponding author
Abstract
Generation of induced oligodendrocyte progenitor cells (iOPCs) from somatic fibroblasts is a strategy for cell-based therapy of myelin diseases. However, iOPC generation is inefficient, and the resulting iOPCs exhibit limited expansion and differentiation competence. Here we overcome these limitations by transducing an optimized transcription factor combination into a permissive donor phenotype, the pericyte. Pericyte-derived iOPCs (PC-iOPCs) are stably expandable and functionally myelinogenic with high differentiation competence. Unexpectedly, however, we found that PC-iOPCs are metastable so that they can produce myelination-competent oligodendrocytes or revert to their original identity in a context-dependent fashion. Phenotypic reversion of PC-iOPCs is tightly linked to memory of their original transcriptome and epigenome. Phenotypic reversion can be disconnected from this donor cell memory effect, and in vivo myelination can eventually be achieved by transplantation of O4+ pre-oligodendrocytes. Our data show that donor cell source and memory can contribute to the fate and stability of directly converted cells.
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