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Whole-genome analysis of human embryonic stem cells enables rational line selection based on genetic variation.

Published version
Peer-reviewed

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Type

Article

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Authors

Merkle, Florian T 
Ghosh, Sulagna 
Genovese, Giulio 
Handsaker, Robert E 
Kashin, Seva 

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.

Description

Keywords

embryonic stem cell, genetic variant, genomics, pluripotent, rational selection, resource, whole-genome sequencing, Genetic Variation, Genome, Human, Human Embryonic Stem Cells, Humans, Nucleotides, Whole Genome Sequencing

Journal Title

Cell Stem Cell

Conference Name

Journal ISSN

1934-5909
1875-9777

Volume Title

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (100574/Z/12/Z)
Medical Research Council (MC_UU_12012/1)
Medical Research Council (MC_UU_12012/5)
Wellcome Trust (105602/Z/14/Z)
Academy of Medical Sciences (Springboard)
Wellcome Trust (211221/Z/18/Z)
Silicon Valley Community Foundation (2018-191942 (5022))
New York Stem Cell Foundation (NYSCF-R-156)
MRC (MR/P501967/1)
Medical Research Council (MR/R015724/1)
Academy of Medical Sciences (SBF001\1016)
National Institute of Neurological Disorders and Stroke (K99NS083713)
MRC (MC_UU_00014/5)
Medical Research Council (MC_PC_12012)
Academy of Medical Sciences, New York Stem Cell Foundation