Matches in SemOpenAlex for { <https://semopenalex.org/work/W2076047032> ?p ?o ?g. }
- W2076047032 endingPage "1139" @default.
- W2076047032 startingPage "1136" @default.
- W2076047032 abstract "The mechanisms involved in the reprogramming of differentiated cells into induced pluripotent stem (iPS) cells by the three transcription factors Oct4 (also known as Pou5f1), Klf4 and Sox2 remain poorly understood. The Ink4/Arf locus comprises the Cdkn2a-Cdkn2b genes encoding three potent tumour suppressors, namely p16(Ink4a), p19(Arf) and p15(Ink4b), which are basally expressed in differentiated cells and upregulated by aberrant mitogenic signals. Here we show that the locus is completely silenced in iPS cells, as well as in embryonic stem (ES) cells, acquiring the epigenetic marks of a bivalent chromatin domain, and retaining the ability to be reactivated after differentiation. Cell culture conditions during reprogramming enhance the expression of the Ink4/Arf locus, further highlighting the importance of silencing the locus to allow proliferation and reprogramming. Indeed, the three factors together repress the Ink4/Arf locus soon after their expression and concomitant with the appearance of the first molecular markers of 'stemness'. This downregulation also occurs in cells carrying the oncoprotein large-T, which functionally inactivates the pathways regulated by the Ink4/Arf locus, thus indicating that the silencing of the locus is intrinsic to reprogramming and not the result of a selective process. Genetic inhibition of the Ink4/Arf locus has a profound positive effect on the efficiency of iPS cell generation, increasing both the kinetics of reprogramming and the number of emerging iPS cell colonies. In murine cells, Arf, rather than Ink4a, is the main barrier to reprogramming by activation of p53 (encoded by Trp53) and p21 (encoded by Cdkn1a); whereas, in human fibroblasts, INK4a is more important than ARF. Furthermore, organismal ageing upregulates the Ink4/Arf locus and, accordingly, reprogramming is less efficient in cells from old organisms, but this defect can be rescued by inhibiting the locus with a short hairpin RNA. All together, we conclude that the silencing of Ink4/Arf locus is rate-limiting for reprogramming, and its transient inhibition may significantly improve the generation of iPS cells." @default.
- W2076047032 created "2016-06-24" @default.
- W2076047032 creator A5035652739 @default.
- W2076047032 creator A5039382465 @default.
- W2076047032 creator A5044099254 @default.
- W2076047032 creator A5050675146 @default.
- W2076047032 creator A5056464877 @default.
- W2076047032 creator A5061302501 @default.
- W2076047032 creator A5077962453 @default.
- W2076047032 creator A5085977927 @default.
- W2076047032 date "2009-08-01" @default.
- W2076047032 modified "2023-10-06" @default.
- W2076047032 title "The Ink4/Arf locus is a barrier for iPS cell reprogramming" @default.
- W2076047032 cites W1583038422 @default.
- W2076047032 cites W1968931043 @default.
- W2076047032 cites W1972134119 @default.
- W2076047032 cites W1980878904 @default.
- W2076047032 cites W1989168159 @default.
- W2076047032 cites W2002179012 @default.
- W2076047032 cites W2014418062 @default.
- W2076047032 cites W2017840637 @default.
- W2076047032 cites W2019818957 @default.
- W2076047032 cites W2027960166 @default.
- W2076047032 cites W2030523067 @default.
- W2076047032 cites W2032580087 @default.
- W2076047032 cites W2035181962 @default.
- W2076047032 cites W2073429636 @default.
- W2076047032 cites W2073759231 @default.
- W2076047032 cites W2076984763 @default.
- W2076047032 cites W2087404852 @default.
- W2076047032 cites W2091865841 @default.
- W2076047032 cites W2095417588 @default.
- W2076047032 cites W2101091611 @default.
- W2076047032 cites W2121619780 @default.
- W2076047032 cites W2125987139 @default.
- W2076047032 cites W2126376889 @default.
- W2076047032 cites W2138977668 @default.
- W2076047032 cites W2153978704 @default.
- W2076047032 cites W2157033538 @default.
- W2076047032 cites W2161191369 @default.
- W2076047032 cites W2165178639 @default.
- W2076047032 cites W2170210082 @default.
- W2076047032 cites W2170569465 @default.
- W2076047032 doi "https://doi.org/10.1038/nature08290" @default.
- W2076047032 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3578184" @default.
- W2076047032 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19668188" @default.
- W2076047032 hasPublicationYear "2009" @default.
- W2076047032 type Work @default.
- W2076047032 sameAs 2076047032 @default.
- W2076047032 citedByCount "878" @default.
- W2076047032 countsByYear W20760470322012 @default.
- W2076047032 countsByYear W20760470322013 @default.
- W2076047032 countsByYear W20760470322014 @default.
- W2076047032 countsByYear W20760470322015 @default.
- W2076047032 countsByYear W20760470322016 @default.
- W2076047032 countsByYear W20760470322017 @default.
- W2076047032 countsByYear W20760470322018 @default.
- W2076047032 countsByYear W20760470322019 @default.
- W2076047032 countsByYear W20760470322020 @default.
- W2076047032 countsByYear W20760470322021 @default.
- W2076047032 countsByYear W20760470322022 @default.
- W2076047032 countsByYear W20760470322023 @default.
- W2076047032 crossrefType "journal-article" @default.
- W2076047032 hasAuthorship W2076047032A5035652739 @default.
- W2076047032 hasAuthorship W2076047032A5039382465 @default.
- W2076047032 hasAuthorship W2076047032A5044099254 @default.
- W2076047032 hasAuthorship W2076047032A5050675146 @default.
- W2076047032 hasAuthorship W2076047032A5056464877 @default.
- W2076047032 hasAuthorship W2076047032A5061302501 @default.
- W2076047032 hasAuthorship W2076047032A5077962453 @default.
- W2076047032 hasAuthorship W2076047032A5085977927 @default.
- W2076047032 hasBestOaLocation W20760470322 @default.
- W2076047032 hasConcept C104317684 @default.
- W2076047032 hasConcept C107459253 @default.
- W2076047032 hasConcept C119056186 @default.
- W2076047032 hasConcept C137338518 @default.
- W2076047032 hasConcept C145103041 @default.
- W2076047032 hasConcept C148738053 @default.
- W2076047032 hasConcept C1491633281 @default.
- W2076047032 hasConcept C167227067 @default.
- W2076047032 hasConcept C2777933648 @default.
- W2076047032 hasConcept C2778265714 @default.
- W2076047032 hasConcept C28328180 @default.
- W2076047032 hasConcept C502942594 @default.
- W2076047032 hasConcept C54355233 @default.
- W2076047032 hasConcept C77255625 @default.
- W2076047032 hasConcept C83640560 @default.
- W2076047032 hasConcept C84597430 @default.
- W2076047032 hasConcept C86803240 @default.
- W2076047032 hasConcept C95444343 @default.
- W2076047032 hasConceptScore W2076047032C104317684 @default.
- W2076047032 hasConceptScore W2076047032C107459253 @default.
- W2076047032 hasConceptScore W2076047032C119056186 @default.
- W2076047032 hasConceptScore W2076047032C137338518 @default.
- W2076047032 hasConceptScore W2076047032C145103041 @default.
- W2076047032 hasConceptScore W2076047032C148738053 @default.
- W2076047032 hasConceptScore W2076047032C1491633281 @default.
- W2076047032 hasConceptScore W2076047032C167227067 @default.