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

doi:10.1016/j.stemcr.2017.03.012

iPSCORE: A Resource of 222 iPSC Lines Enabling Functional Characterization of Genetic Variation across a Variety of Cell Types

Stem Cell Reports. 2017 Apr 11;8(4):1086-1100. doi: 10.1016/j.stemcr.2017.03.012.

Authors

Athanasia D Panopoulos¹, Matteo D'Antonio², Paola Benaglio³, Roy Williams⁴, Sherin I Hashem⁵, Bernhard M Schuldt⁶, Christopher DeBoever⁷, Angelo D Arias³, Melvin Garcia², Bradley C Nelson⁵, Olivier Harismendy⁸, David A Jakubosky⁹, Margaret K R Donovan⁷, William W Greenwald⁷, KathyJean Farnam², Megan Cook², Victor Borja², Carl A Miller², Jonathan D Grinstein¹⁰, Frauke Drees³, Jonathan Okubo², Kenneth E Diffenderfer¹¹, Yuriko Hishida¹, Veronica Modesto¹¹, Carl T Dargitz¹¹, Rachel Feiring¹¹, Chang Zhao², Aitor Aguirre⁵, Thomas J McGarry⁵, Hiroko Matsui², He Li², Joaquin Reyna², Fangwen Rao⁵, Daniel T O'Connor⁵, Gene W Yeo¹², Sylvia M Evans⁵, Neil C Chi¹³, Kristen Jepsen², Naoki Nariai³, Franz-Josef Müller⁶, Lawrence S B Goldstein¹⁴, Juan Carlos Izpisua Belmonte¹, Eric Adler⁵, Jeanne F Loring¹⁵, W Travis Berggren¹¹, Agnieszka D'Antonio-Chronowska², Erin N Smith³, Kelly A Frazer¹⁶

Affiliations

¹ Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
² Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
³ Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA.
⁴ 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.
⁵ Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
⁶ Zentrum für Integrative Psychiatrie, Universitätsklinikum Schleswig-Holstein, 24105 Kiel, Germany.
⁷ Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA.
⁸ 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.
⁹ Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA.
¹⁰ 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.
¹¹ Stem Cell Core, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
¹² 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.
¹³ 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.
¹⁴ Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
¹⁵ Center for Regenerative Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
¹⁶ 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. Electronic address: [email protected].

Abstract

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.

Keywords: GWAS; KCNH2; LQT2; NHLBI Next Gen; cardiac disease; iPSC; iPSC-derived cardiomyocytes; iPSCORE; molecular traits; physiological traits.

Published by Elsevier Inc.

MeSH terms

Arrhythmias, Cardiac / ethnology
Arrhythmias, Cardiac / genetics*
Arrhythmias, Cardiac / metabolism
Arrhythmias, Cardiac / physiopathology
Cell Differentiation
Cell Line
Cellular Reprogramming / genetics
Databases, Factual*
Genetic Association Studies*
Genetic Variation*
Genotype
High-Throughput Nucleotide Sequencing
Humans
Induced Pluripotent Stem Cells / cytology
Induced Pluripotent Stem Cells / metabolism*
Multigene Family
Myocytes, Cardiac / cytology
Myocytes, Cardiac / metabolism*
Oligonucleotide Array Sequence Analysis
Phenotype
Polymorphism, Single Nucleotide
Racial Groups

Abstract

MeSH terms

Grants and funding