1.3. Stem cell quality and culture adaptation with reference to cancer

Principles of stem cell biology and cancer: future applications and therapeutics. Edited by T. Regad, T. J. Sayers and R. C. Rees. John Wiley & Sons (2015)

1.3.1. Genomic abnormalities Chromosomal aberrations Copy-number variations Single-nucleotide variations

1.3.2. Epigenetics Imprinting and XCI Methylation pattern Histone modifications

1.3.3. hESC culture adaptation with reference to cancer (genomic and epigenetic) Impact of hESC culture-induced genomic and epigenetic changes in differentiated cells

In the embryo, during normal development, the cells of the ICM usually exist for just a few days before differentiating into more mature cell types to form the three germ layers. During the derivation of human embryonic stem cell lines, cells from the ICM of a blastocyst are transferred to a culture dish and need to adapt to this in vitro environment. Prolonged culture of these cells exposes them to various stress factors, which can then lead to further selection of the most adapted cells. Initially, this process of adaptation occurs mostly through epigenetic mechanisms, as in vitro-cultured mESCs can convert back to form a normal mouse embryo in vivo. However, with extended laboratory culture for months or years (as is possible with pluripotent stem cells), selection of cells that have increased survival may occur, further helping their culture adaptation. This can lead to not only epigenetic but also genomic changes in the cell population.

Any genetic or epigenetic changes that occur in hESCs over extended culture may alter their developmental potential, function or behaviour and should therefore be avoided, if possible. In particular, nonreversible genomic changes need to be tracked and controlled to minimize effects on experimental studies or treatments.


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