The key role of H3K27me3 demethylase kdm6 family in the regulation of human neurogenesis was revealed

Pan Guangjin, research group of Guangzhou Institute of biomedicine and health, Chinese Academy of Sciences, published a research paper entitled jmjd3 and UTX determine fidelity and lineage specification of human natural agent cells in nature communications In this study, it was found that H3K27me3 demethylase jmjd3 and UTX play a necessary and consistent role in the maintenance of human neural stem cells and the fate specialization of neural subtypes Neurogenesis is a continuous and highly ordered process, which is a process from pluripotent stem cells to neural stem cells and a variety of specialized cell lineages such as neurons and glial cells It plays a key role in the development of human embryos Epigenetic modification plays an important role in maintaining cell characteristics and determining cell fate However, the precise epigenetic regulation mechanism of human neurogenesis is not clear In September 2017, pan Guangjin's research team reported on nature communications the key role of polycombin complex 2 (PRC2), which performs the function of H3K27me3 methyltransferase, in the formation of human neuroectoderm However, the role and exact mechanism of H3K27me3 demethylase kdm6 family (jmjd3 / kdm6b and UTX / kdm6a) in the regulation of human neurogenesis have not been elucidated It has been found that kdm6s (jmjd3 and / or UTX) knockout human embryonic stem cells can form neural stem cells normally, but the proliferation ability of human neural stem cells is weakened and can not effectively differentiate into neurons and glial cells In mechanism, jmjd3 and UTX are enriched in genes related to neural development, and knockout of kdm6 results in H3K27me3 accumulation of these genes and decrease of DNA accessibility This study revealed the different needs of kdm6s in specialized neural stem cells and neural sub cells, and emphasized the important role of single epigenetic regulator in cell fate determination This study revealed the key role of kdm6s dependent H3K27me3 demethylation in the fidelity and fate determination of specific lineage in human neurogenesis Combined with the key role of PRC2 specific neuroectoderm reported earlier by the research group, this series of studies elucidated the different needs of H3K27me3 methylation and demethylation in the continuous lineage specialization from pluripotent stem cells to neural subtypes during human neurogenesis This series of research also provides a reference for exploring the regulation of cell fate determination, the molecular mechanism of the occurrence and development of nervous system related diseases and finding new therapeutic targets (BIOON Com)