한빛사 논문
Kee-Pyo Kim1, You Wu2, Juyong Yoon1,*, Kenjiro Adachi1,†, Guangming Wu1,3,‡, Sergiy Velychko1, Caitlin M. MacCarthy1, Borami Shin1, Albrecht Röpke4, Marcos J. Arauzo-Bravo5,6, Martin Stehling7, Dong Wook Han8, Yawei Gao2, Johnny Kim9, Shaorong Gao2 and Hans R. Schöler1,10,§
1Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, Münster 48149, Germany.
2Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
3Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kai Yuan Avenue, Science Park, Guangzhou 510530, China.
4Institute of Human Genetics, University of Münster, Vesaliusweg 12-14, Münster 48149, Germany.
5Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastian 20014, Spain.
6IKERBASQUE, Basque Foundation for Science, Bilbao 48011, Spain.
7Flow Cytometry Unit, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, Münster 48149, Germany.
8School of Biotechnology and Healthcare, Wuyi University, Jiangmen 529020, China.
9Department of Cardiac Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim 61231, Germany.
10University of Münster, Medical Faculty, Domagkstrasse 3, Münster 48149, Germany.
§Corresponding author.
*Present address: Department of Early Discovery, Ksilink, 16 rue d’Ankara, 67000 Strasbourg, France.
†Present address: Astellas Pharma Inc., 5-2-3 Tokodai, Tsukuba-shi, Ibaraki 300-2698, Japan.
‡Present address: Guangzhou Regenerative Medicine and Health Guangdong Laboratory LEDY Building 3, Kaiyuan Avenue 188, Hangpu District, Guangzhou 510320, P.R. China.
Abstract
OCT4 (also known as POU5F1) plays an essential role in reprogramming. It is the only member of the POU (Pit-Oct-Unc) family of transcription factors that can induce pluripotency despite sharing high structural similarities to all other members. Here, we discover that OCT6 (also known as POU3F1) can elicit reprogramming specifically in human cells. OCT6-based reprogramming does not alter the mesenchymal-epithelial transition but is attenuated through the delayed activation of the pluripotency network in comparison with OCT4-based reprogramming. Creating a series of reciprocal domain-swapped chimeras and mutants across all OCT factors, we clearly delineate essential elements of OCT4/OCT6-dependent reprogramming and, conversely, identify the features that prevent induction of pluripotency by other OCT factors. With this strategy, we further discover various chimeric proteins that are superior to OCT4 in reprogramming. Our findings clarify how reprogramming competences of OCT factors are conferred through their structural components.
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