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5-Aza-2?-Deoxycytidine and Valproic Acid in Combination with CHIR99021 and A83-01 Induce Pluripotency Genes Expression in Human Adult Somatic Cells

dc.contributor.authorAguirre Vazquez, Alain Jesús
dc.contributor.authorSalazar Olivo, Luis Antonio
dc.contributor.authorFlores Ponce, Xóchitl Natalia
dc.contributor.authorArriaga Guerrero, Ana Leticia
dc.contributor.authorGarza Rodríguez, Dariela
dc.contributor.authorCamacho Moll, María Elena
dc.contributor.authorVelasco, Iván
dc.contributor.authorCastorena Torres, Fabiola
dc.contributor.authorDadheech, Nidheesh
dc.contributor.authorBermúdez de León, Mario Abelardo
dc.date.accessioned2022-03-10T19:33:41Z
dc.date.available2022-03-10T19:33:41Z
dc.date.issued2021
dc.identifier.citationAguirre-Vázquez, A.; Salazar-Olivo, L.A.; Flores-Ponce, X.; Arriaga-Guerrero, A.L.; Garza-Rodríguez, D.; Camacho-Moll, M.E.; Velasco, I.; Castorena-Torres, F.; Dadheech, N.; Bermúdez de León, M. 5-Aza-2?-Deoxycytidine and Valproic Acid in Combination with CHIR99021 and A83-01 Induce Pluripotency Genes Expression in Human Adult Somatic Cells. Molecules 2021, 26, 1909. https://doi.org/10.3390/molecules26071909
dc.identifier.urihttp://hdl.handle.net/11627/5768
dc.description.abstract"A generation of induced pluripotent stem cells (iPSC) by ectopic expression of OCT4, SOX2, KLF4, and c-MYC has established promising opportunities for stem cell research, drug discovery, and disease modeling. While this forced genetic expression represents an advantage, there will always be an issue with genomic instability and transient pluripotency genes reactivation that might preclude their clinical application. During the reprogramming process, a somatic cell must undergo several epigenetic modifications to induce groups of genes capable of reactivating the endogenous pluripotency core. Here, looking to increase the reprograming efficiency in somatic cells, we evaluated the effect of epigenetic molecules 5-aza-2?-deoxycytidine (5AZ) and valproic acid (VPA) and two small molecules reported as reprogramming enhancers, CHIR99021 and A83-01, on the expression of pluripotency genes and the methylation profile of the OCT4 promoter in a human dermal fibroblasts cell strain. The addition of this cocktail to culture medium increased the expression of OCT4, SOX2, and KLF4 expression by 2.1-fold, 8.5-fold, and 2-fold, respectively, with respect to controls; concomitantly, a reduction in methylated CpG sites in OCT4 promoter region was observed. The epigenetic cocktail also induced the expression of the metastasis-associated gene S100A4. However, the epigenetic cocktail did not induce the morphological changes characteristic of the reprogramming process. In summary, 5AZ, VPA, CHIR99021, and A83-01 induced the expression of OCT4 and SOX2, two critical genes for iPSC. Future studies will allow us to precise the mechanisms by which these compounds exert their reprogramming effects."
dc.publisherMDPI
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectReprogramming
dc.subject5-aza-2?-deoxycytidine
dc.subjectValproic acid
dc.subjectStem cells
dc.subjectEpigenetics
dc.subject.classificationBIOLOGÍA MOLECULAR
dc.title5-Aza-2?-Deoxycytidine and Valproic Acid in Combination with CHIR99021 and A83-01 Induce Pluripotency Genes Expression in Human Adult Somatic Cells
dc.typearticle
dc.identifier.doihttps://doi.org/10.3390/molecules26071909
dc.rights.accessAcceso Abierto


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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 Internacional