Short Telomeres in ESCs Lead to Unstable Differentiation
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TLDR
An unexpected role of functional telomeres is demonstrated in the genome-wide epigenetic regulation of cell differentiation and a potentially important role of telomere instability in cell fate during development or disease is suggested.About:
This article is published in Cell Stem Cell.The article was published on 2013-04-04 and is currently open access. It has received 77 citations till now. The article focuses on the topics: Homeobox protein NANOG & Leukemia inhibitory factor.read more
Citations
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DNA methylation-based biomarkers and the epigenetic clock theory of ageing
Steve Horvath,Ken Raj +1 more
TL;DR: Biomarkers of ageing based on DNA methylation data enable accurate age estimates for any tissue across the entire life course and link developmental and maintenance processes to biological ageing, giving rise to a unified theory of life course.
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Impact of genomic damage and ageing on stem cell function
TL;DR: The impact of the various types of DNA damage that accumulate with ageing on stem cell functionality, as well as the development of cancer, is reviewed.
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Aneuploidy induces profound changes in gene expression, proliferation and tumorigenicity of human pluripotent stem cells
Uri Ben-David,Gal Arad,Uri Weissbein,Berhan Mandefro,Adva Maimon,Tamar Golan-Lev,Kavita Narwani,Amander T. Clark,Peter W. Andrews,Nissim Benvenisty,Juan Carlos Biancotti +10 more
TL;DR: Comparison of proliferation, differentiation and apoptosis between diploid and aneuploid hPSC shows that trisomy 12 significantly increases the proliferation rate of hPSCs, mainly as a consequence of increased replication.
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The fetal programming of telomere biology hypothesis: an update.
TL;DR: It is proposed that the effects of suboptimal intrauterine conditions on the initial setting of telomere length and telomerase expression/activity capacity may be mediated by the programming actions of stress-related maternal–placental–fetal oxidative, immune, endocrine and metabolic pathways in a manner that may ultimately accelerate cellular dysfunction, ageing and disease susceptibility over the lifespan.
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Quality control: Genome maintenance in pluripotent stem cells
TL;DR: In this paper, the authors focused on potential means to alleviate the genomic insults experienced by PSCs, and to detect them as soon as they arise, in order to prevent the detrimental consequences of these genomic aberrations on PSC application in basic research and regenerative medicine.
References
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DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development.
TL;DR: It is demonstrated that two recently identified DNA methyltransferases, DnMT3a and Dnmt3b, are essential for de novo methylation and for mouse development and play important roles in normal development and disease.
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Targeted mutation of the DNA methyltransferase gene results in embryonic lethality.
TL;DR: Results indicate that while a 3-fold reduction in levels of genomic m5C has no detectable effect on the viability or proliferation of ES cells in culture, a similar reduction of DNA methylation in embryos causes abnormal development and embryonic lethality.
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Nanog safeguards pluripotency and mediates germline development.
Ian Chambers,José C. R. Silva,Douglas Colby,Jennifer Nichols,Jennifer Nichols,Bianca Nijmeijer,Morag Robertson,Jan Vrána,Kenneth Jones,Kenneth Jones,Lars Grotewold,Austin Smith +11 more
TL;DR: By genetic deletion, it is shown that, although they are prone to differentiate, embryonic stem cells can self-renew indefinitely in the permanent absence of Nanog, and it is surmised that Nanog stabilizes embryonicstem cells in culture by resisting or reversing alternative gene expression states.
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An extended transcriptional network for pluripotency of embryonic stem cells
TL;DR: This work identified target promoters of nine transcription factors, including somatic cell reprogramming factors (Oct4, Sox2, Klf4, and c-Myc) and others and broadly distinguish targets of c- myc versus other factors on a global scale in mouse ES cells.
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Dissecting self-renewal in stem cells with RNA interference
Natalia Ivanova,Radu Dobrin,Rong Lu,Iulia Kotenko,John Levorse,Christina DeCoste,Xenia Schafer,Yi Lun,Ihor R. Lemischka +8 more
TL;DR: This work uses short hairpin RNA (shRNA) loss-of-function techniques to downregulate a set of gene products whose expression patterns suggest self-renewal regulatory functions, and focuses on transcriptional regulators and identifies seven genes for which shRNA-mediated depletion negatively affects self-Renewal.