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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 | |
ALAIN JESUS AGUIRRE VAZQUEZ Luis Antonio Salazar Olivo XOCHITL NATALIA FLORES PONCE ANA LETICIA ARRIAGA GUERRERO Dariela Garza Rodríguez MARIA ELENA CAMACHO MOLL Ivan Velasco FABIOLA CASTORENA TORRES Nidheesh Dadheech MARIO ABELARDO BERMUDEZ DE LEON | |
Acceso Abierto | |
Atribución-NoComercial-SinDerivadas | |
https://doi.org/10.3390/molecules26071909 | |
Reprogramming 5-aza-2′-deoxycytidine Valproic acid Stem cells Epigenetics | |
"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." | |
MDPI | |
2021 | |
Artículo | |
Aguirre-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 | |
BIOLOGÍA MOLECULAR | |
Versión publicada | |
publishedVersion - Versión publicada | |
Aparece en las colecciones: | Publicaciones Científicas Biología Molecular |
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