GSE169395
Next Generation Sequencing Facilitates Quantitative Analysis of Wild Type and EedcKO Forebrain Transcriptomes
The histone methyltransferase complex PRC2 is a crucial chromatin modifier and controls key steps in developmental transitions and cell fate choices. Mutations in PRC2 core subunits are found in Weaver syndrome with craniofacial defects, intellectual disabilities, and often macrocephaly, but its pathogenicity and molecular mechanism are unknown. Here, we examined the role of PRC2/Eed in neural stem/progenitor cells (NSPCs) during cortical neurogenesis We found that Eed is highly expressed in embryonic cerebral cortex and specific deletion of Eed in forebrain reduced the number of upper layer neurons but not deeper layer neurons and ultimately contributed to abnormal cortical development. In addition, our results revealed that PRC2/Eed regulated Hedgehog signaling pathway through activation of Gli3 not dependent on H3K27me3 but H3K27ac. What?s more, Increased Gli3 in NSPCs could reduce Gli1 expression and contribute to the defects of cortical neurogenesis caused by Eed deletion. Finally, Hedgehog signaling activation with small molecule SAG or genetic inactivation of Ptch1 could partially rescue the cortical neurogenesis defects in vivo after Eed depletion. In general, we identified a novel PRC2/Eed-Gli3-Gli1 regulatory axis that is critical for normal cortical neurogenesis. Our findings define a critical function for PRC2/Eed in cortical development and shed light on the genetic basis of intellectual disabilities of neural developmental disorders caused by PRC2/Eed mutation. Overall design: We report the forebrain RNA-seq data of wild type and EedcKO littermate mice at E12.5. We mapped about 30 million sequence reads per sample to the mouse genome (build mm10). By comparing the sequencing data of mice in the wild time group and the EedcKO group, the transcriptome map of Eed deletion can be obtained. These data are useful for the study of Eed in early neurodevelopment. Examination of 2 different group in E12.5 forbrain tissues..