Li, C.; Han, X.; Wang, J.; Liu, F.; Zhang, Y.; Li, Z.; Lu, Z.; Yue, Y.; Xiang, J.; Li, X. Mixed-Lineage Leukemia 1 Inhibition Enhances the Differentiation Potential of Bovine Embryonic Stem Cells by Increasing H3K4 Mono-Methylation at Active Promoters. Int. J. Mol. Sci.2023, 24, 11901.
Li, C.; Han, X.; Wang, J.; Liu, F.; Zhang, Y.; Li, Z.; Lu, Z.; Yue, Y.; Xiang, J.; Li, X. Mixed-Lineage Leukemia 1 Inhibition Enhances the Differentiation Potential of Bovine Embryonic Stem Cells by Increasing H3K4 Mono-Methylation at Active Promoters. Int. J. Mol. Sci. 2023, 24, 11901.
Li, C.; Han, X.; Wang, J.; Liu, F.; Zhang, Y.; Li, Z.; Lu, Z.; Yue, Y.; Xiang, J.; Li, X. Mixed-Lineage Leukemia 1 Inhibition Enhances the Differentiation Potential of Bovine Embryonic Stem Cells by Increasing H3K4 Mono-Methylation at Active Promoters. Int. J. Mol. Sci.2023, 24, 11901.
Li, C.; Han, X.; Wang, J.; Liu, F.; Zhang, Y.; Li, Z.; Lu, Z.; Yue, Y.; Xiang, J.; Li, X. Mixed-Lineage Leukemia 1 Inhibition Enhances the Differentiation Potential of Bovine Embryonic Stem Cells by Increasing H3K4 Mono-Methylation at Active Promoters. Int. J. Mol. Sci. 2023, 24, 11901.
Abstract
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, named bESCs-F7) were established from the in vitro fertilized (IVF) embryos by Wnt signaling inhibition, while its contribution to 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 improves the pluripotency and differentiation potentials of bESCs via up-regulation of stem cell signaling pathways such as PI3K-Akt and WNT. MLL1 inhibition decreases H3K4me1 modification at promoters in bESCs and altered the distribution of DNA methylation in bESCs. In summary, MLL1 inhibition enables bESCs to acquire better pluripotency, and its application may provide high quality pluripotent stem cells for domestic animals.
Biology and Life Sciences, Cell and Developmental Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
