Genetic Variation, Not Cell Type of Origin, Underlies Regulatory Differences in iPSCs

作者: Courtney L Kagan , Nicholas E Banovich , Bryan J Pavlovic , Kristen Patterson , Irene Gallego Romero

DOI: 10.1101/013888

关键词:

摘要: The advent of induced pluripotent stem cells (iPSCs) revolutionized Human Genetics by allowing us to generate from easily accessible somatic tissues. This technology can have immense implications for regenerative medicine, but iPSCs also represent a paradigm shift in the study complex human phenotypes, including gene regulation and disease. Yet, an unresolved caveat iPSC model system is extent which reprogrammed retain residual phenotypes their precursor cells. To directly address this issue, we used effective design compare regulatory between derived two types commonly We show that cell type origin only minimally affects expression levels DNA methylation iPSCs. Instead, genetic variation main driver differences different donors.

参考文章(36)
Shinya Yamanaka, Kazutoshi Takahashi, Induction of pluripotent stem cells from mouse fibroblast cultures Tanpakushitsu kakusan koso. Protein nucleic acid enzyme. ,vol. 51, pp. 2346- 2351 ,(2006)
Edgar Z. Palmer, Mordecai Ezekiel, Methods of correlation analysis Southern Economic Journal. ,vol. 94, pp. 249- ,(1931) , 10.2307/1052503
Zhumur Ghosh, Kitchener D. Wilson, Yi Wu, Shijun Hu, Thomas Quertermous, Joseph C. Wu, Persistent Donor Cell Gene Expression among Human Induced Pluripotent Stem Cells Contributes to Differences with Human Embryonic Stem Cells PLoS ONE. ,vol. 5, pp. e8975- ,(2010) , 10.1371/JOURNAL.PONE.0008975
Franz-Josef Müller, Bernhard M Schuldt, Roy Williams, Dylan Mason, Gulsah Altun, Eirini P Papapetrou, Sandra Danner, Johanna E Goldmann, Arne Herbst, Nils O Schmidt, Josef B Aldenhoff, Louise C Laurent, Jeanne F Loring, A bioinformatic assay for pluripotency in human cells Nature Methods. ,vol. 8, pp. 315- 317 ,(2011) , 10.1038/NMETH.1580
Mark H. Chin, Mike J. Mason, Wei Xie, Stefano Volinia, Mike Singer, Cory Peterson, Gayane Ambartsumyan, Otaren Aimiuwu, Laura Richter, Jin Zhang, Ivan Khvorostov, Vanessa Ott, Michael Grunstein, Neta Lavon, Nissim Benvenisty, Carlo M. Croce, Amander T. Clark, Tim Baxter, April D. Pyle, Mike A. Teitell, Matteo Pelegrini, Kathrin Plath, William E. Lowry, Induced Pluripotent Stem Cells and Embryonic Stem Cells Are Distinguished by Gene Expression Signatures Cell Stem Cell. ,vol. 5, pp. 111- 123 ,(2009) , 10.1016/J.STEM.2009.06.008
Wing Y. Chang, Kamal Garcha, Janet L. Manias, William L. Stanford, Deciphering the complexities of human diseases and disorders by coupling induced-pluripotent stem cells and systems genetics Wiley Interdisciplinary Reviews: Systems Biology and Medicine. ,vol. 4, pp. 339- 350 ,(2012) , 10.1002/WSBM.1170
Sara E. Howden, Hady Wardan, Lucille Voullaire, Samuel McLenachan, Robert Williamson, Panos Ioannou, Jim Vadolas, Chromatin-binding regions of EBNA1 protein facilitate the enhanced transfection of Epstein-Barr virus-based vectors. Human Gene Therapy. ,vol. 17, pp. 833- 844 ,(2006) , 10.1089/HUM.2006.17.833
Foad Rouhani, Natsuhiko Kumasaka, Miguel Cardoso de Brito, Allan Bradley, Ludovic Vallier, Daniel Gaffney, Genetic Background Drives Transcriptional Variation in Human Induced Pluripotent Stem Cells PLoS Genetics. ,vol. 10, pp. e1004432- ,(2014) , 10.1371/JOURNAL.PGEN.1004432
Rebecca Josowitz, Xonia Carvajal-Vergara, Ihor R Lemischka, Bruce D Gelb, Induced pluripotent stem cell-derived cardiomyocytes as models for genetic cardiovascular disorders. Current Opinion in Cardiology. ,vol. 26, pp. 223- 229 ,(2011) , 10.1097/HCO.0B013E32834598AD
Keisuke Okita, Yasuko Matsumura, Yoshiko Sato, Aki Okada, Asuka Morizane, Satoshi Okamoto, Hyenjong Hong, Masato Nakagawa, Koji Tanabe, Ken-ichi Tezuka, Toshiyuki Shibata, Takahiro Kunisada, Masayo Takahashi, Jun Takahashi, Hiroh Saji, Shinya Yamanaka, A more efficient method to generate integration-free human iPS cells Nature Methods. ,vol. 8, pp. 409- 412 ,(2011) , 10.1038/NMETH.1591