Human iPSC-derived retinal pigment epithelium: a model system for identifying and functionally characterizing causal variants at AMD risk loci
作者： Erin N Smith , Agnieszka D’Antonio-Chronowska , William W Greenwald , Victor Borja , Lana R Aguiar
DOI: 10.1101/440230
关键词:
摘要: Summary We evaluate whether human induced pluripotent stem cell-derived retinal pigment epithelium (iPSC-RPE) cells can be used to prioritize and functionally characterize causal variants at age-related macular degeneration (AMD) risk loci. generated iPSC-RPE from six subjects show that they have morphological molecular characteristics similar native RPE. RNA-seq, ATAC-seq, H3K27ac ChIP-seq data observe high similarity in gene expression enriched transcription factor motif profiles between fetal-RPE. performed fine-mapping of AMD loci by integrating the iPSC-RPE, adult retina, RPE, which identified rs943080 as probable variant VEGFA. is associated with altered chromatin accessibility a distal ATAC-seq peak, decreased overall VEGFA, allele specific non-coding transcript. These results provide insight into mechanism underlying association VEGFA locus AMD.
sci-hub.st 参考文章(44)
GTEx Consortium, Kristin G Ardlie, David S Deluca, Ayellet V Segrè, Timothy J Sullivan, Taylor R Young, Ellen T Gelfand, Casandra A Trowbridge, Julian B Maller, Taru Tukiainen, Monkol Lek, Lucas D Ward, Pouya Kheradpour, Benjamin Iriarte, Yan Meng, Cameron D Palmer, Tõnu Esko, Wendy Winckler, Joel N Hirschhorn, Manolis Kellis, Daniel G MacArthur, Gad Getz, Andrey A Shabalin, Gen Li, Yi-Hui Zhou, Andrew B Nobel, Ivan Rusyn, Fred A Wright, Tuuli Lappalainen, Pedro G Ferreira, Halit Ongen, Manuel A Rivas, Alexis Battle, Sara Mostafavi, Jean Monlong, Michael Sammeth, Marta Mele, Ferran Reverter, Jakob M Goldmann, Daphne Koller, Roderic Guigó, Mark I McCarthy, Emmanouil T Dermitzakis, Eric R Gamazon, Hae Kyung Im, Anuar Konkashbaev, Dan L Nicolae, Nancy J Cox, Timothée Flutre, Xiaoquan Wen, Matthew Stephens, Jonathan K Pritchard, Zhidong Tu, Bin Zhang, Tao Huang, Quan Long, Luan Lin, Jialiang Yang, Jun Zhu, Jun Liu, Amanda Brown, Bernadette Mestichelli, Denee Tidwell, Edmund Lo, Mike Salvatore, Saboor Shad, Jeffrey A Thomas, John T Lonsdale, Michael T Moser, Bryan M Gillard, Ellen Karasik, Kimberly Ramsey, Christopher Choi, Barbara A Foster, John Syron, Johnell Fleming, Harold Magazine, Rick Hasz, Gary D Walters, Jason P Bridge, Mark Miklos, Susan Sullivan, Laura K Barker, Heather M Traino, Maghboeba Mosavel, Laura A Siminoff, Dana R Valley, Daniel C Rohrer, Scott D Jewell, Philip A Branton, Leslie H Sobin, Mary Barcus, Liqun Qi, Jeffrey McLean, Pushpa Hariharan, Ki Sung Um, Shenpei Wu, David Tabor, Charles Shive, Anna M Smith, Stephen A Buia, Anita H Undale, Karna L Robinson, Nancy Roche, Kimberly M Valentino, Angela Britton, Robin Burges, Debra Bradbury, Kenneth W Hambright, John Seleski, Greg E Korzeniewski, Kenyon Erickson, Yvonne Marcus, Jorge Tejada, Mehran Taherian, Chunrong Lu, Margaret Basile, Deborah C Mash, Simona Volpi, Jeffery P Struewing, Gary F Temple, Joy Boyer, Deborah Colantuoni, Roger Little, Susan Koester, Latarsha J Carithers, Helen M Moore, Ping Guan, Carolyn Compton, Sherilyn J Sawyer, Joanne P Demchok, Jimmie B Vaught, Chana A Rabiner, Nicole C Lockhart, Kristin G Ardlie, Gad Getz, Fred A Wright, Manolis Kellis, Simona Volpi, Emmanouil T Dermitzakis, None, The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans Science. ,vol. 348, pp. 648- 660 ,(2015) , 10.1126/SCIENCE.1262110
Evangelos S. Gragoudas, Anthony P. Adamis, Emmett T. Cunningham, Matthew Feinsod, David R. Guyer, Pegaptanib for Neovascular Age-Related Macular Degeneration The New England Journal of Medicine. ,vol. 351, pp. 2805- 2816 ,(2004) , 10.1056/NEJMOA042760
Kati Kinnunen, Goran Petrovski, Morten C. Moe, András Berta, Kai Kaarniranta, Molecular mechanisms of retinal pigment epithelium damage and development of age‐related macular degeneration Acta Ophthalmologica. ,vol. 90, pp. 299- 309 ,(2012) , 10.1111/J.1755-3768.2011.02179.X
Partho Sarothi Ray, Jie Jia, Peng Yao, Mithu Majumder, Maria Hatzoglou, Paul L. Fox, A stress-responsive RNA switch regulates VEGFA expression. Nature. ,vol. 457, pp. 915- 919 ,(2009) , 10.1038/NATURE07598
Ke Tang, Sophia Y. Tsai, Ming-Jer Tsai, COUP-TFs and eye development. Biochimica et Biophysica Acta. ,vol. 1849, pp. 201- 209 ,(2015) , 10.1016/J.BBAGRM.2014.05.022
Oleg Mayba, Houston N Gilbert, Jinfeng Liu, Peter M Haverty, Suchit Jhunjhunwala, Zhaoshi Jiang, Colin Watanabe, Zemin Zhang, MBASED: allele-specific expression detection in cancer tissues and cell lines Genome Biology. ,vol. 15, pp. 405- 405 ,(2014) , 10.1186/S13059-014-0405-3
Toshihide Kurihara, Peter D. Westenskow, Stephen Bravo, Edith Aguilar, Martin Friedlander, Targeted deletion of Vegfa in adult mice induces vision loss Journal of Clinical Investigation. ,vol. 122, pp. 4213- 4217 ,(2012) , 10.1172/JCI65157
Frank W. Albert, Leonid Kruglyak, The role of regulatory variation in complex traits and disease Nature Reviews Genetics. ,vol. 16, pp. 197- 212 ,(2015) , 10.1038/NRG3891
J. Zhang, Disruption of gradient expression of Zic3 resulted in abnormal intra-retinal axon projection. Development. ,vol. 131, pp. 1553- 1562 ,(2004) , 10.1242/DEV.01041
Bo Li, Colin N Dewey, RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome BMC Bioinformatics. ,vol. 12, pp. 323- 323 ,(2011) , 10.1186/1471-2105-12-323