Genomic alterations in cultured human embryonic stem cells

Anirban Maitra, Dan E. Arking, Narayan Shivapurkar, Morna Ikeda, Victor Stastny, Keyaunoosh Kassauei, Guoping Sui, David J. Cutler, Ying Liu, Sandii N. Brimble, Karin Noaksson, Johan Hyllner, Thomas C. Schulz, Xianmin Zeng, William J. Freed, Jeremy Crook, Suman Abraham, Alan Colman, Peter Sartipy, Sei Ichi MatsuiMelissa Carpenter, Adi F. Gazdar, Mahendra Rao, Aravinda Chakravarti

Research output: Contribution to journalArticle

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Abstract

Cultured human embryonic stem cell (hESC) lines are an invaluable resource because they provide a uniform and stable genetic system for functional analyses and therapeutic applications. Nevertheless, these dividing cells, like other cells, probably undergo spontaneous mutation at a rate of 10-9 per nucleotide. Because each mutant has only a few progeny, the overall biological properties of the cell culture are not altered unless a mutation provides a survival or growth advantage. Clonal evolution that leads to emergence of a dominant mutant genotype may potentially affect cellular phenotype as well. We assessed the genomic fidelity of paired early- and late-passage hESC lines in the course of tissue culture. Relative to early-passage lines, eight of nine late-passage hESC lines had one or more genomic alterations commonly observed in human cancers, including aberrations in copy number (45%), mitochondrial DNA sequence (22%) and gene promoter methylation (90%), although the latter was essentially restricted to 2 of 14 promoters examined. The observation that hESC lines maintained in vitro develop genetic and epigenetic alterations implies that periodic monitoring of these lines will be required before they are used in in vivo applications and that some late-passage hESC lines may be unusable for therapeutic purposes.

Original languageEnglish (US)
Pages (from-to)1099-1103
Number of pages5
JournalNature Genetics
Volume37
Issue number10
DOIs
StatePublished - Oct 2005

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Cell Line
Clonal Evolution
Mutation
Mitochondrial DNA
Epigenomics
Methylation
Nucleotides
Cell Culture Techniques
Genotype
Human Embryonic Stem Cells
Phenotype
Survival
Therapeutics
Growth
Genes
Neoplasms

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Maitra, A., Arking, D. E., Shivapurkar, N., Ikeda, M., Stastny, V., Kassauei, K., ... Chakravarti, A. (2005). Genomic alterations in cultured human embryonic stem cells. Nature Genetics, 37(10), 1099-1103. https://doi.org/10.1038/ng1631

Genomic alterations in cultured human embryonic stem cells. / Maitra, Anirban; Arking, Dan E.; Shivapurkar, Narayan; Ikeda, Morna; Stastny, Victor; Kassauei, Keyaunoosh; Sui, Guoping; Cutler, David J.; Liu, Ying; Brimble, Sandii N.; Noaksson, Karin; Hyllner, Johan; Schulz, Thomas C.; Zeng, Xianmin; Freed, William J.; Crook, Jeremy; Abraham, Suman; Colman, Alan; Sartipy, Peter; Matsui, Sei Ichi; Carpenter, Melissa; Gazdar, Adi F.; Rao, Mahendra; Chakravarti, Aravinda.

In: Nature Genetics, Vol. 37, No. 10, 10.2005, p. 1099-1103.

Research output: Contribution to journalArticle

Maitra, A, Arking, DE, Shivapurkar, N, Ikeda, M, Stastny, V, Kassauei, K, Sui, G, Cutler, DJ, Liu, Y, Brimble, SN, Noaksson, K, Hyllner, J, Schulz, TC, Zeng, X, Freed, WJ, Crook, J, Abraham, S, Colman, A, Sartipy, P, Matsui, SI, Carpenter, M, Gazdar, AF, Rao, M & Chakravarti, A 2005, 'Genomic alterations in cultured human embryonic stem cells', Nature Genetics, vol. 37, no. 10, pp. 1099-1103. https://doi.org/10.1038/ng1631
Maitra A, Arking DE, Shivapurkar N, Ikeda M, Stastny V, Kassauei K et al. Genomic alterations in cultured human embryonic stem cells. Nature Genetics. 2005 Oct;37(10):1099-1103. https://doi.org/10.1038/ng1631
Maitra, Anirban ; Arking, Dan E. ; Shivapurkar, Narayan ; Ikeda, Morna ; Stastny, Victor ; Kassauei, Keyaunoosh ; Sui, Guoping ; Cutler, David J. ; Liu, Ying ; Brimble, Sandii N. ; Noaksson, Karin ; Hyllner, Johan ; Schulz, Thomas C. ; Zeng, Xianmin ; Freed, William J. ; Crook, Jeremy ; Abraham, Suman ; Colman, Alan ; Sartipy, Peter ; Matsui, Sei Ichi ; Carpenter, Melissa ; Gazdar, Adi F. ; Rao, Mahendra ; Chakravarti, Aravinda. / Genomic alterations in cultured human embryonic stem cells. In: Nature Genetics. 2005 ; Vol. 37, No. 10. pp. 1099-1103.
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