Whole-genome analysis of human embryonic stem cells enables rational line selection based on genetic variation.
View / Open Files
Authors
Merkle, Florian T
Ghosh, Sulagna
Genovese, Giulio
Handsaker, Robert E
Kashin, Seva
Meyer, Daniel
Karczewski, Konrad J
O'Dushlaine, Colm
Pato, Carlos
Pato, Michele
MacArthur, Daniel G
McCarroll, Steven A
Eggan, Kevin
Publication Date
2022-03-03Journal Title
Cell Stem Cell
ISSN
1934-5909
Publisher
Elsevier BV
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Merkle, F. T., Ghosh, S., Genovese, G., Handsaker, R. E., Kashin, S., Meyer, D., Karczewski, K. J., et al. (2022). Whole-genome analysis of human embryonic stem cells enables rational line selection based on genetic variation.. Cell Stem Cell https://doi.org/10.1016/j.stem.2022.01.011
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.
Sponsorship
Academy of Medical Sciences, New York Stem Cell Foundation
Funder references
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)
Identifiers
External DOI: https://doi.org/10.1016/j.stem.2022.01.011
This record's URL: https://www.repository.cam.ac.uk/handle/1810/333402
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.
Recommended or similar items
The current recommendation prototype on the Apollo Repository will be turned off on 03 February 2023. Although the pilot has been fruitful for both parties, the service provider IKVA is focusing on horizon scanning products and so the recommender service can no longer be supported. We recognise the importance of recommender services in supporting research discovery and are evaluating offerings from other service providers. If you would like to offer feedback on this decision please contact us on: support@repository.cam.ac.uk