ArticleMolecules (Basel, Switzerland)2021
5-Aza-2'-Deoxycytidine and Valproic Acid in Combination with CHIR99021 and A83-01 Induce Pluripotency Genes Expression in Human Adult Somatic Cells.
Article in Molecules (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
- Enhanced small intestinal organoid-derived epithelial cell adhesion and growth in organ-on-a-chip devices.RSC advances · 2025Article
- Revealing the pathogenesis of gastric intestinal metaplasia based on the mucosoid air-liquid interface.Journal of translational medicine · 2024Article
- Chemical approaches targeting the hurdles of hepatocyte transplantation: mechanisms, applications, and advances.Frontiers in cell and developmental biology · 2024Review
- Ascorbic acid and salvianolic acid B enhance the valproic acid and 5-azacytidinemediated cardiac differentiation of mesenchymal stem cells.Molecular biology reports · 2023Article
- Cell-type dependent regulation of pluripotency and chromatin remodeling genes by hydralazine.Stem cell research & therapy · 2023Article
- Application of Small Molecules in the Central Nervous System Direct Neuronal Reprogramming.Frontiers in bioengineering and biotechnology · 2022Review
- 5-Aza combined with VPA reprograms human T lineage acute leukemia Jurkat cells into B-cell-like cells by epigenetic activation of PAX5.Biotechnology progressArticle
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
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.
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