title: Dynamic changes in the copy number of pluripotency and cell proliferation genes in human ESCs and iPSCs during reprogramming and time in culture.
abstract: Genomic stability is critical for the clinical use of human embryonic and induced pluripotent stem cells. We performed high-resolution SNP (single-nucleotide polymorphism) analysis on 186 pluripotent and 119 nonpluripotent samples. We report a higher frequency of subchromosomal copy number variations in pluripotent samples compared to nonpluripotent samples, with variations enriched in specific genomic regions. The distribution of these variations differed between hESCs and hiPSCs, characterized by large numbers of duplications found in a few hESC samples and moderate numbers of deletions distributed across many hiPSC samples. For hiPSCs, the reprogramming process was associated with deletions of tumor-suppressor genes, whereas time in culture was associated with duplications of oncogenic genes. We also observed duplications that arose during a differentiation protocol. Our results illustrate the dynamic nature of genomic abnormalities in pluripotent stem cells and the need for frequent genomic monitoring to assure phenotypic stability and clinical safety.
authors.affiliation: Department of Reproductive Medicine, University of California, San Diego, La Jolla, CA 92093, USA. llaurent@ucsd.edu
authors.forename: Louise C
authors.initials: LC
authors.lastname: Laurent
authors.forename: Igor
authors.initials: I
authors.lastname: Ulitsky
authors.forename: Ileana
authors.initials: I
authors.lastname: Slavin
authors.forename: Ha
authors.initials: H
authors.lastname: Tran
authors.forename: Andrew
authors.initials: A
authors.lastname: Schork
authors.forename: Robert
authors.initials: R
authors.lastname: Morey
authors.forename: Candace
authors.initials: C
authors.lastname: Lynch
authors.forename: Julie V
authors.initials: JV
authors.lastname: Harness
authors.forename: Sunray
authors.initials: S
authors.lastname: Lee
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Barrero
authors.forename: Sherman
authors.initials: S
authors.lastname: Ku
authors.forename: Marina
authors.initials: M
authors.lastname: Martynova
authors.forename: Ruslan
authors.initials: R
authors.lastname: Semechkin
authors.forename: Vasiliy
authors.initials: V
authors.lastname: Galat
authors.forename: Joel
authors.initials: J
authors.lastname: Gottesfeld
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Izpisua Belmonte
authors.forename: Chuck
authors.initials: C
authors.lastname: Murry
authors.forename: Hans S
authors.initials: HS
authors.lastname: Keirstead
authors.forename: Hyun-Sook
authors.initials: HS
authors.lastname: Park
authors.forename: Uli
authors.initials: U
authors.lastname: Schmidt
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Laslett
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Muller
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Nievergelt
authors.forename: Ron
authors.initials: R
authors.lastname: Shamir
authors.forename: Jeanne F
authors.initials: JF
authors.lastname: Loring
mesh_terms: D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D018628:Gene Dosage; D015894:Genome, Human; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism