Study reveals the regulatory mechanism of microglia development

Microglia are the innate immune cells in the brain, which are the important immune defense lines to protect the brain from the invasion and destruction of virus and bacteria Microglia also play an important role in brain injury, inflammation and neurodegenerative diseases Microglia play an important role in the whole stage of brain development in addition to the physiological and pathological conditions of adulthood These important functions of microglia are related to the specific spatial and temporal distribution of microglia in the embryonic cerebral cortex However, it is not clear how microglia develop in the brain during neurogenesis and whether neural stem cells will affect the development of microglia Jiao Jianwei research group, Institute of zoology, Chinese Academy of Sciences, observed and stained the brains of mouse embryos at different stages It was found that microglia were distributed in the abundant ependymal and subependymal regions (VZ / SVZ) of neural stem cells in the early embryonic brains, but almost no in the cortex At the same time, it was observed that the histone variant H2A Z.2 was abundantly expressed in neural stem cells in the VZ / SVZ region In order to further study whether knocking out H2A Z.2 in neural stem cells can regulate the development of early microglia, researchers found that knocking out H2A Z.2 in neural stem cells can cause the abnormal increase of microglia in VZ / SVZ area It was also found that the absence of H2A Z.2 promoted the transformation of radial glial cells into intermediate precursor cells By sequencing the RNA SEQ of H2A Z.2 knockout mice, the researchers found that H2A Z.2 can regulate the secretion of chemokine CXCL14 in neural stem cells It has been proved for the first time that the chemokine CXCL14 plays an important role in regulating the development of brain microglia As one of the most important histone variants, H2A Z.2 affects chromatin structure to participate in many biological processes, such as transcriptional regulation, chromosome separation, heterochromatin formation and genome stability H2A Z.2 regulates the transcription of CXCL14 by recruiting the promoter region of H3K9 methyltransferase G9a to CXCL14, thereby affecting the development of microglia This study shows that the neural stem cells mediated by the apparent regulatory molecule H2A Z.2 play a key role in regulating the early development of microglia, broadening the understanding of the interaction between two different types of cells in the central nervous system, and providing a new idea for the exploration of neuroimmune related diseases On November 11, the related research results published in the Journal of the National Academy of Sciences (PNAs) a research paper entitled "natural contributor cells mediated by H2A Z.2 regular micro development via CXCL14 in the empirical brain" in the way of direct submission