Epigenetic Instability in ES Cells and Cloned Mice

By David Humpherys, K. Eggan, H. Akutsu, K. Hochedlinger, W. Rideout, D. Biniszkiewicz, R. Yanagimachi, R. Jaenisch. Science, 2001

741 citations recorded by the source corpus.

Subfields: Genetics, Molecular Biology, Public Health, Environmental and Occupational Health

View Paper: https://www.semanticscholar.org/paper/8c99346e247928adc7867d959d72d124b43e2ee0

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Citations in the corpus

Rapid changes in clonal lines: the death of a 'sacred cow' (2003, background): “Such changes cause a reduction in the survival of individual embryos or adults per se, the longevity of animals born to term, and their immunological competence (Wakayama et al., 2000; De Sousa et al., 2001; Humpherys et al., 2001; Cibelli et al., 2002).”
Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals (2003, background): “The few cloned mice that do survive show dysregulation of many imprinted and non-imprinted genes regardless of the type of donor nucleu”
Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19. (2003, background): “…(M16) undergo epigenetic alterations in the H19, IGF2, Grb10, and Grb7 genes (Khosla et al. 2001); mouse embryos cultured in Whitten’s medium can undergo LOI of H19 (Doherty et al. 2000); and cloned mice show variations in several imprinted genes in the resulting embryos (Humpherys et al. 2001).”
Epigenetic reprogramming in mammals. (2005, background): “Epigenetic defects described in cloned offspring include errors in X inactivation (79,80), imprinting (78,81,82), DNA methylation in general and of specific gene and repeat sequences (17,78,83,84), histone acetylation and methylation (54) and widespread alterations in gene expression (85) including ”
Characterization of human embryonic stem cell lines by the International Stem Cell Initiative (2007, background): “Imprinted genes, whose parent-of-origin–dependent expression is epigenetically regulated, have variable allele-specific expression and methylation patterns in some mES cell”
Somatic cell reprogramming and transitions between pluripotent states: facts, hypotheses, unresolved issues (2010, neutral): “Further, aberrant and variable imprinting are evident in cloned mice and in ESC lines derived from embryos (Humpherys et al., 2001), indicating that even substantial deregulation of genes still allows development to birth and beyond.”
Neoliberalism on the molecular scale. Economic and genetic reductionism in biotechnology battles (2003, background): “Who among non-scientists would guess––having heard the praise of genomics ‘‘precision’’––that most of the cells or embryos into which technicians attempt to insert new genetic material are killed, or are deformed, or fail to take up the new genetic construct, or carry the ‘‘gene’’ yet fail to expres”
DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA (2007, background): “ES cells show much higher rates of de novo methylation than do differentiated somatic cells, and methylation imprints are gained and lost at high rates in ES cells8,9.”
The promise of induced pluripotent stem cells in research and therapy (2012, background): “The subcloning of ES cells has revealed genetic and epigenetic anomalies that would probably have otherwise gone undetected in the heterogeneous ES-cell populatio”
DNA methylation and healthy human aging (2015, background): “epigenetically divergent upon multiple passages (Humpherys et al., 2001).”
A maternal-zygotic effect gene Zfp57 maintains both maternal and paternal imprints (2008, methodology): “Mouse ES cells were used as a model system because they display high de novo methylation activities (Humpherys et al., 2001; Lei et al., 1996; Ooi et al., 2007).”