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Series GSE72442 Query DataSets for GSE72442
Status Public on Sep 10, 2016
Title Chd8 mediates cortical neurogenesis through transcriptional regulation of cell cycle and Wnt signaling genes  
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary De novo mutations in CHD8 are strongly associated with autism spectrum disorder (ASD), however the underlying mechanisms remain elusive. Here we report that Chd8 knockdown during cortical development results in defective neural progenitor proliferation and differentiation that ultimately manifests in abnormal neuronal morphology and behaviors in adult mice. Transcriptome analysis revealed that on the one hand Chd8 stimulates the transcription of cell cycle genes, while on the other it precludes the induction of neural specific genes by regulating the expression of PRC2 complex components. Furthermore, knockdown of Chd8 disrupts the expression of key transducers of Wnt signaling, and enhancing Wnt signaling rescues the transcriptional and behavioral deficits caused by Chd8 knockdown. We propose that these roles of Chd8 and the dynamics of its expression during development help negotiate the fine balance between neural progenitor proliferation and differentiation. Together, these observations provide new insights into the etiology of ASD.
Overall design In utero electroporation of cortical radial glial cells with either control or Chd8 shRNA. Cortices from 3-5 embryos were pooled per biological replicates (three biological replicates for Chd8 sh1, and two biological replicates for Chd8 sh2), followed by FAC sorting of GFP positive cells.
Contributor(s) Durak O, Gao F, Tsai L
Citation(s) 27694995
Submission date Aug 27, 2015
Last update date May 15, 2019
Contact name Li-Huei Tsai
Phone 617-324-1660
Organization name MIT
Department Picower Institute for Learning and Memory
Lab Li-Huei Tsai
Street address 77 Mass Ave # 46-4235
City Cambridge
State/province Massachusetts
ZIP/Postal code 02139
Country USA
Platforms (2)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (10)
GSM1862740 RNA-Seq CTRL1
GSM1862741 RNA-Seq CTRL2
GSM1862742 RNA-Seq CHD8_KD1
BioProject PRJNA294075
SRA SRP062904

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Supplementary file Size Download File type/resource
GSE72442_FPKM_shRNA1.txt.gz 449.4 Kb (ftp)(http) TXT
GSE72442_FPKM_shRNA2.txt.gz 350.9 Kb (ftp)(http) TXT
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