Copy number variant hotspots in Han Taiwanese population induced pluripotent stem cell lines - lessons from establishing the Taiwan human disease iPSC Consortium Bank

• Published in: Journal of biomedical science 2020-09, Vol.27 (1), p.1-92, Article 92
• Main Authors: Huang, Ching-Ying, Li, Ling-Hui, Hsu, Wan-Tseng, Cheng, Yu-Che, Nicholson, Martin W., Liu, Chun-Lin, Ting, Chien-Yu, Ko, Hui-Wen, Syu, Shih-Han, Wen, Cheng-Hao, Yan, Zhuge, Huang, Hsiang-Po, Su, Hong-Lin, Chiang, Po-Min, Shen, Chia-Ning, Chen, Hsin-Fu, Yen, B. Lin Ju, Lu, Huai-En, Hwang, Shiaw-Min, Chiou, Shih-Hwa, Ho, Hong-Nerng, Wu, Jer-Yuarn, Kamp, Timothy J., Wu, Joseph C., Hsieh, Patrick C. H.
• Format: Article
• Language: English
• Subjects: Antibodies; Banks (Finance); Cardiomyocytes; Cell cycle; Cell differentiation; Cell lines; Cell therapy; Chromosomes; Comparative analysis; Consortia; Copy number; Copy number variant; Deoxyribonucleic acid; Disease; DNA; Drug screening; Gene expression; Genomes; Genomics; Hotspot; Human induced pluripotent stem cell; Macular degeneration; Myocardium; Pluripotency; R&D; Research & development; Single-nucleotide polymorphism; Stem cell bank; Stem cells
• ISSN: 1423-0127; 1021-7770; 1423-0127
• DOI: 10.1186/s12929-020-00682-7

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