Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Embryonic stem cells and somatic cells differ in mutation frequency and type.

Authors: Cervantes, Rachel B; Stringer, James R; Shao, Changshun; Tischfield, Jay A; Stambrook, Peter J

Published In Proc Natl Acad Sci U S A, (2002 Mar 19)

Abstract: Pluripotent embryonic stem (ES) cells have been used to produce genetically modified mice as experimental models of human genetic diseases. Increasingly, human ES cells are being considered for their potential in the treatment of injury and disease. Here we have shown that mutation in murine ES cells, heterozygous at the selectable Aprt locus, differs from that in embryonic somatic cells. The mutation frequency in ES cells is significantly lower than that in mouse embryonic fibroblasts, which is similar to that in adult cells in vivo. The distribution of spontaneous mutagenic events is remarkably different between the two cell types. Although loss of the functional allele is the predominant mutation type in both cases, representing about 80% of all events, mitotic recombination accounted for all loss of heterozygosity events detected in somatic cells. In contrast, mitotic recombination in ES cells appeared to be suppressed and chromosome loss/reduplication, leading to uniparental disomy (UPD), represented more than half of the loss of heterozygosity events. Extended culture of ES cells led to accumulation of cells with adenine phosphoribosyltransferase deficiency and UPD. Because UPD leads to reduction to homozygosity at multiple recessive disease loci, including tumor suppressor loci, in the affected chromosome, the increased risk of tumor formation after stem cell therapy should be viewed with concern.

PubMed ID: 11891338 Exiting the NIEHS site

MeSH Terms: Adenine Phosphoribosyltransferase/genetics; Animals; Blastocyst/cytology*; Blastocyst/enzymology; Blastocyst/metabolism; Cell Line; Chromosome Painting; Comparative Study; Crosses, Genetic; Female; Fibroblasts/cytology; Fibroblasts/enzymology; Fibroblasts/metabolism*; Gene Frequency/genetics*; Genotype; Hypoxanthine Phosphoribosyltransferase/genetics; Kinetics; Loss of Heterozygosity/genetics; Male; Mice; Mutation/genetics*; Nondisjunction, Genetic; Recombination, Genetic/genetics; Research Support, U.S. Gov't, P.H.S.; Stem Cells/cytology; Stem Cells/enzymology; Stem Cells/metabolism*; Uniparental Disomy/genetics

Back
to Top