- 作者: Ching-Ying Huang, Ling-Hui Li, Wan-Tseng Hsu, Yu-Che Cheng, Martin W. Nicholson, Chun-Lin Liu, Chien-Yu Ting, Hui-Wen Ko, Shih-Han Syu, Cheng-Hao Wen, Zhuge Yan, Hsiang-Po Huang, Hong-Lin Su, Po-Min Chiang, Chia-Ning Shen, Hsin-Fu Chen, B. Lin Ju Yen, Huai-En Lu, Shiaw-Min Hwang, Shih-Hwa Chiou, Hong-Nerng Ho, Jer-Yuarn Wu, Timothy J. Kamp, Joseph C. Wu & Patrick C. H. Hsieh
- 作者服務機構: 1. Institute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan 2. School of Pharmacy, College of Medicine, National Taiwan University, Taipei, 100, Taiwan 3. Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, 300, Taiwan 4. Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA 5. Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, 100, Taiwan 6. Department of Life Sciences, National Chung-Hsing University, Taichung, 402, Taiwan 7. Institute of Clinical Medicine, National Cheng Kung University, Tainan, 701, Taiwan 8. Genomics Research Center, Academia Sinica, Taipei, 115, Taiwan 9. Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, 350, Taiwan 10. Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, 112, Taiwan 11. Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University, Taipei, Taiwan 12. Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI, 53705, USA
- 中文摘要:
- 英文摘要:
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. - 中文關鍵字:
- 英文關鍵字: Human induced pluripotent stem cell, Cell differentiation, Stem cell bank, Drug screening, Copy number variant, Hotspot