Copy number variant hotspots in Han Taiwanese population induced pluripotent stem cell lines - lessons from establishing
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(2020) 27:92
RESEARCH
Open Access
Copy number variant hotspots in Han Taiwanese population induced pluripotent stem cell lines - lessons from establishing the Taiwan human disease iPSC Consortium Bank Ching-Ying Huang1, Ling-Hui Li1, Wan-Tseng Hsu2, Yu-Che Cheng1, Martin W. Nicholson1, Chun-Lin Liu1, Chien-Yu Ting1, Hui-Wen Ko3, Shih-Han Syu3, Cheng-Hao Wen3, Zhuge Yan4, Hsiang-Po Huang5, Hong-Lin Su6, Po-Min Chiang7, Chia-Ning Shen8, Hsin-Fu Chen5, B. Lin Ju Yen9, Huai-En Lu3, Shiaw-Min Hwang3, Shih-Hwa Chiou10, Hong-Nerng Ho11, Jer-Yuarn Wu1, Timothy J. Kamp12, Joseph C. Wu4 and Patrick C. H. Hsieh1*
Abstract Background: The Taiwan Human Disease iPSC Service Consortium was established to accelerate Taiwan’s growing stem cell research initiatives and provide a platform for researchers interested in utilizing induced pluripotent stem cell (iPSC) technology. The consortium has generated and characterized 83 iPSC lines: 11 normal and 72 disease iPSC lines covering 21 different diseases, several of which are of high incidence in Taiwan. Whether there are any reprogramming-induced recurrent copy number variant (CNV) hotspots in iPSCs is still largely unknown. Methods: We performed genome-wide copy number variant screening of 83 Han Taiwanese iPSC lines and compared them with 1093 control subjects using an Affymetrix genome-wide human SNP array. Results: In the iPSCs, we identified ten specific CNV loci and seven “polymorphic” CNV regions that are associated with the reprogramming process. Additionally, we established several differentiation protocols for our iPSC lines. We demonstrated that our iPSC-derived cardiomyocytes respond to pharmacological agents and were successfully engrafted into the mouse myocardium demonstrating their potential application in cell therapy. Conclusions: The CNV hotspots induced by cell reprogramming have successfully been identified in the current study. This finding may be used as a reference index for evaluating iPSC quality for future clinical applications. Our aim was to establish a national iPSC resource center generating iPSCs, made available to researchers, to benefit the stem cell community in Taiwan and throughout the world. Keywords: Human induced pluripotent stem cell, Cell differentiation, Stem cell bank, Drug screening, Copy number variant, Hotspot
* Correspondence: [email protected] 1 Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the mate
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