Mixed-Lineage Leukemia 1 Inhibition Enhances the Differentiation Potential of Bovine Embryonic Stem Cells by Increasing H3K4 Mono-Methylation at Active Promoters.
Chen LiXuejie HanJing WangFang LiuYuanyuan ZhangZihong LiZhenyu LuYongli YueJinzhu XiangXueling LiPublished in: International journal of molecular sciences (2023)
Mixed-lineage leukemia 1 (MLL1) introduces 1-, 2- and 3-methylation into histone H3K4 through the evolutionarily conserved set domain. In this study, bovine embryonic stem cells (bESCs, known as bESCs-F7) were established from in vitro-fertilized (IVF) embryos via Wnt signaling inhibition; however, their contribution to the endoderm in vivo is limited. To improve the quality of bESCs, MM-102, an inhibitor of MLL1, was applied to the culture. The results showed that MLL1 inhibition along with GSK3 and MAP2K inhibition (3i) at the embryonic stage did not affect bESCs' establishment and pluripotency. MLL1 inhibition improved the pluripotency and differentiation potential of bESCs via the up-regulation of stem cell signaling pathways such as PI3K-Akt and WNT. MLL1 inhibition decreased H3K4me1 modification at the promoters and altered the distribution of DNA methylation in bESCs. In summary, MLL1 inhibition gives bESCs better pluripotency, and its application may provide high-quality pluripotent stem cells for domestic animals.
Keyphrases
- epithelial mesenchymal transition
- signaling pathway
- embryonic stem cells
- acute myeloid leukemia
- pi k akt
- dna methylation
- stem cells
- protein protein
- gene expression
- genome wide
- induced apoptosis
- pregnant women
- small molecule
- single cell
- climate change
- cell death
- cell cycle arrest
- endoplasmic reticulum stress
- human health
- copy number