Histone demethylase KDM6A promotes somatic cell reprogramming by epigenetically regulating the PTEN and IL-6 signal pathways
| Autor: | Zhiyan Shan, Qi Jiang, Xing-Wei Huang, Lei Lei, Guangming Wu, Yanshuang Wu, Xinglin Hu |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Cell signaling Somatic cell Induced Pluripotent Stem Cells Epigenesis Genetic Mice 03 medical and health sciences 0302 clinical medicine Animals Humans Epigenetics Induced pluripotent stem cell Epigenomics Histone Demethylases biology Interleukin-6 PTEN Phosphohydrolase Cell Biology Cellular Reprogramming Cell biology Mice Inbred C57BL HEK293 Cells 030104 developmental biology Histone Mice Inbred DBA biology.protein Molecular Medicine Demethylase Female Reprogramming 030217 neurology & neurosurgery Signal Transduction Developmental Biology |
| Zdroj: | Stem Cells. 38:960-972 |
| ISSN: | 1549-4918 1066-5099 |
| DOI: | 10.1002/stem.3188 |
| Popis: | Aberrant epigenetic reprogramming is one of the major barriers for somatic cell reprogramming. Although our previous study has indicated that H3K27me3 demethylase KDM6A can improve the nuclear reprogramming efficiency, the mechanism remains unclear. In this study, we demonstrate that the overexpression of Kdm6a may improve induced pluripotent stem cell (iPSC) reprogramming efficiency in a demethylase enzymatic activity-dependent manner. KDM6A erased H3K27me3 on pluripotency- and metabolism-related genes, and consequently facilitated changing the gene expression profile and metabolic pattern to an intermediate state. Furthermore, KDM6A may promote IL-6 expression, and the secreted IL-6 may further improve iPSC reprogramming efficiency. In addition, KDM6A may promote PTEN expression to decrease p-AKT and p-mTOR levels, which in turn facilitates reprogramming. Overall, our results reveal that KDM6A may promote iPSC reprogramming efficiency by accelerating changes in the gene expression profile and the metabolic pattern in a demethylation-activity-dependent manner. These results may provide an insight into the relationship between epigenomics, transcriptomics, metabolomics, and reprogramming. |
| Databáze: | OpenAIRE |
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