title: Adaptation to culture of human embryonic stem cells and oncogenesis in vivo.
abstract: The application of human embryonic stem cells (HESCs) to provide differentiated cells for regenerative medicine will require the continuous maintenance of the undifferentiated stem cells for long periods in culture. However, chromosomal stability during extended passaging cannot be guaranteed, as recent cytogenetic studies of HESCs have shown karyotypic aberrations. The observed karyotypic aberrations probably reflect the progressive adaptation of self-renewing cells to their culture conditions. Genetic change that increases the capacity of cells to proliferate has obvious parallels with malignant transformation, and we propose that the changes observed in HESCs in culture reflect tumorigenic events that occur in vivo, particularly in testicular germ cell tumors. Further supporting a link between culture adaptation and malignancy, we have observed the formation of a chromosomal homogeneous staining region in one HESC line, a genetic feature almost a hallmark of cancer cells. Identifying the genes critical for culture adaptation may thus reveal key players for both stem cell maintenance in vitro and germ cell tumorigenesis in vivo.
authors.affiliation: Sheffield Regional Cytogenetics Service, Sheffield Children's Trust, Western Bank, Sheffield S10 2TH, UK.
authors.forename: Duncan E C
authors.initials: DE
authors.lastname: Baker
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Harrison
authors.forename: Edna
authors.initials: E
authors.lastname: Maltby
authors.forename: Kath
authors.initials: K
authors.lastname: Smith
authors.forename: Harry D
authors.initials: HD
authors.lastname: Moore
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Shaw
authors.forename: Paul R
authors.initials: PR
authors.lastname: Heath
authors.forename: Hazel
authors.initials: H
authors.lastname: Holden
authors.forename: Peter W
authors.initials: PW
authors.lastname: Andrews
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology*; D002869:Chromosome Aberrations; D053595:Embryonic Stem Cells / Q000473:pathology* / Q000502:physiology*; D006801:Humans; D008957:Models, Genetic