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

Journal: 
Stem Cell Reports
Publication Year: 
2017
Authors: 
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 Muller
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
PubMed link: 
28410642
Public 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.
Scientific 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.