Stem Cell Reports (Apr 2017)
iPSCORE: A Resource of 222 iPSC Lines Enabling Functional Characterization of Genetic Variation across a Variety of Cell Types
- Athanasia D. Panopoulos,
- Matteo D'Antonio,
- Paola Benaglio,
- Roy Williams,
- Sherin I. Hashem,
- Bernhard M. Schuldt,
- Christopher DeBoever,
- Angelo D. Arias,
- Melvin Garcia,
- Bradley C. Nelson,
- Olivier Harismendy,
- David A. Jakubosky,
- Margaret K.R. Donovan,
- William W. Greenwald,
- KathyJean Farnam,
- Megan Cook,
- Victor Borja,
- Carl A. Miller,
- Jonathan D. Grinstein,
- Frauke Drees,
- Jonathan Okubo,
- Kenneth E. Diffenderfer,
- Yuriko Hishida,
- Veronica Modesto,
- Carl T. Dargitz,
- Rachel Feiring,
- Chang Zhao,
- Aitor Aguirre,
- Thomas J. McGarry,
- Hiroko Matsui,
- He Li,
- Joaquin Reyna,
- Fangwen Rao,
- Daniel T. O'Connor,
- Gene W. Yeo,
- Sylvia M. Evans,
- Neil C. Chi,
- Kristen Jepsen,
- Naoki Nariai,
- Franz-Josef Müller,
- Lawrence S.B. Goldstein,
- Juan Carlos Izpisua Belmonte,
- Eric Adler,
- Jeanne F. Loring,
- W. Travis Berggren,
- Agnieszka D'Antonio-Chronowska,
- Erin N. Smith,
- Kelly A. Frazer
Affiliations
- Athanasia D. Panopoulos
- Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
- Matteo D'Antonio
- Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA
- Paola Benaglio
- Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA
- Roy Williams
- Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA; Center for Regenerative Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
- Sherin I. Hashem
- Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
- Bernhard M. Schuldt
- Zentrum für Integrative Psychiatrie, Universitätsklinikum Schleswig-Holstein, 24105 Kiel, Germany
- Christopher DeBoever
- Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA
- Angelo D. Arias
- Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA
- Melvin Garcia
- Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA
- Bradley C. Nelson
- Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
- Olivier Harismendy
- Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA
- David A. Jakubosky
- Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA
- Margaret K.R. Donovan
- Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA
- William W. Greenwald
- Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA
- KathyJean Farnam
- Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA
- Megan Cook
- Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA
- Victor Borja
- Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA
- Carl A. Miller
- Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA
- Jonathan D. Grinstein
- Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA
- Frauke Drees
- Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA
- Jonathan Okubo
- Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA
- Kenneth E. Diffenderfer
- Stem Cell Core, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
- Yuriko Hishida
- Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
- Veronica Modesto
- Stem Cell Core, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
- Carl T. Dargitz
- Stem Cell Core, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
- Rachel Feiring
- Stem Cell Core, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
- Chang Zhao
- Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA
- Aitor Aguirre
- Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
- Thomas J. McGarry
- Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
- Hiroko Matsui
- Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA
- He Li
- Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA
- Joaquin Reyna
- Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA
- Fangwen Rao
- Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
- Daniel T. O'Connor
- Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
- Gene W. Yeo
- Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA
- Sylvia M. Evans
- Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
- Neil C. Chi
- Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA
- Kristen Jepsen
- Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA
- Naoki Nariai
- Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA
- Franz-Josef Müller
- Zentrum für Integrative Psychiatrie, Universitätsklinikum Schleswig-Holstein, 24105 Kiel, Germany
- Lawrence S.B. Goldstein
- Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA
- Juan Carlos Izpisua Belmonte
- Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
- Eric Adler
- Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
- Jeanne F. Loring
- Center for Regenerative Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
- W. Travis Berggren
- Stem Cell Core, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
- Agnieszka D'Antonio-Chronowska
- Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA
- Erin N. Smith
- Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA
- Kelly A. Frazer
- Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA; Corresponding author
- Journal volume & issue
-
Vol. 8,
no. 4
pp. 1086 – 1100
Abstract
Summary: Large-scale collections of induced pluripotent stem cells (iPSCs) could serve as powerful model systems for examining how genetic variation affects biology and disease. Here we describe the iPSCORE resource: a collection of systematically derived and characterized iPSC lines from 222 ethnically diverse individuals that allows for both familial and association-based genetic studies. iPSCORE lines are pluripotent with high genomic integrity (no or low numbers of somatic copy-number variants) as determined using high-throughput RNA-sequencing and genotyping arrays, respectively. Using iPSCs from a family of individuals, we show that iPSC-derived cardiomyocytes demonstrate gene expression patterns that cluster by genetic background, and can be used to examine variants associated with physiological and disease phenotypes. The iPSCORE collection contains representative individuals for risk and non-risk alleles for 95% of SNPs associated with human phenotypes through genome-wide association studies. Our study demonstrates the utility of iPSCORE for examining how genetic variants influence molecular and physiological traits in iPSCs and derived cell lines. : Working as part of the NHLBI NextGen consortium, Panopoulos and colleagues report the derivation and characterization of 222 publicly available iPSCs from ethnically diverse individuals with corresponding genomic data including SNP arrays, RNA-seq, and whole-genome sequencing. This collection provides a powerful resource to investigate the function of genetic variants. Keywords: iPSCORE, iPSC, GWAS, molecular traits, physiological traits, cardiac disease, NHLBI Next Gen, LQT2, KCNH2, iPSC-derived cardiomyocytes
