5-Aza-2′-Deoxycytidine and Valproic Acid in Combination with CHIR99021 and A83-01 Induce Pluripotency Genes Expression in Human Adult Somatic Cells
| Autor: | Xóchitl Flores-Ponce, Maria E. Camacho-Moll, Dariela Garza-Rodríguez, Iván Velasco, Luis A. Salazar-Olivo, Mario Bermúdez de León, Ana Leticia Arriaga-Guerrero, Fabiola Castorena-Torres, Alain Aguirre-Vázquez, Nidheesh Dadheech |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Thiosemicarbazones
5-aza-2′-deoxycytidine Pyridines Somatic cell Gene Expression Pharmaceutical Science Biology Decitabine Article Cell Line Epigenesis Genetic Analytical Chemistry lcsh:QD241-441 Kruppel-Like Factor 4 03 medical and health sciences 0302 clinical medicine lcsh:Organic chemistry SOX2 valproic acid stem cells Drug Discovery Humans Epigenetics Physical and Theoretical Chemistry Induced pluripotent stem cell 030304 developmental biology 0303 health sciences epigenetics fungi Organic Chemistry reprogramming Cell Differentiation Fibroblasts Cell biology Pyrimidines Chemistry (miscellaneous) KLF4 030220 oncology & carcinogenesis embryonic structures Pyrazoles Molecular Medicine Ectopic expression Stem cell Reprogramming |
| Zdroj: | Molecules Volume 26 Issue 7 Molecules, Vol 26, Iss 1909, p 1909 (2021) |
| ISSN: | 1420-3049 |
| DOI: | 10.3390/molecules26071909 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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