SETD8−/− Inhibit Hematopoietic Differentiation in Human Embryonic Stem Cells
Wang Ding, Li Yapu, Huang Xin, Ma Yige, Guo Qing, Zhao Yanhong, Wang Bingrui, Xu Changlu, Zhang Yingnan, Shi Lihong*
Epigenetic regulation is a well-known way to control gene expression. It has been reported that epigenetic regulation could participate in a variety of biological processes such as stem cell pluripotency, cell cycle, lineage differentiation and the functions of many epigenetic factors have been elucidated. However, there are still some epigenetic factors has not been thoroughly studied. SETD8 (KMT5A, lysine methyltransferase 5A)is a protein-lysine N-methyltransferase which can monomethylate Lys-20 of histone H4 and also involve in the regulation of cell cycle, p53-mediated DNA damage and other processes. But, whether it can directly regulate the pluripotency and lineage differentiation of human embryonic stem cells (hESCs) has not been reported. In this study, we used CRISPR/Cas9 gene editing technology to knock out SETD8 in hESCs. Functional studies showed that the knockout of SETD8 significantly reduced the expression levels of pluripotent genes OCT4 and NANOG, and inhibited the hematopoietic development process of hESCs in vitro. We also used siRNAs to knock down STED8 during different stages of hematopoietic development, and found that the hematopoietic development process was inhibited. This result confirmed that SETD8 could regulate hematopoietic development in vitro at various stages.
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