Whole-genome Analysis of Human Embryonic Stem Cells Enables Rational Line Selection Based on Genetic Variation

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2022 Feb 17

PMID 35176222

Authors

Florian T Merkle

Sulagna Ghosh

Giulio Genovese

Robert E Handsaker

Seva Kashin

Daniel Meyer

Konrad J Karczewski

Colm ODushlaine

Carlos Pato

Michele Pato

Daniel G MacArthur

Steven A McCarroll

Kevin Eggan

Affiliations

Soon will be listed here.

Abstract

Despite their widespread use in research, there has not yet been a systematic genomic analysis of human embryonic stem cell (hESC) lines at a single-nucleotide resolution. We therefore performed whole-genome sequencing (WGS) of 143 hESC lines and annotated their single-nucleotide and structural genetic variants. We found that while a substantial fraction of hESC lines contained large deleterious structural variants, finer-scale structural and single-nucleotide variants (SNVs) that are ascertainable only through WGS analyses were present in hESC genomes and human blood-derived genomes at similar frequencies. Moreover, WGS allowed us to identify SNVs associated with cancer and other diseases that could alter cellular phenotypes and compromise the safety of hESC-derived cellular products transplanted into humans. As a resource to enable reproducible hESC research and safer translation, we provide a user-friendly WGS data portal and a data-driven scheme for cell line maintenance and selection.

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