GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE129644 Query DataSets for GSE129644
Status Public on Apr 12, 2019
Title Elevated Endothelial Sox2 Causes Lumen Disruption and Cerebral AVMs
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Lumen integrity in vascularization requires fully differentiated endothelial cells (ECs). Here, we report that endothelial-mesenchymal transitions (EndMTs) emerged in ECs of cerebral arteriovenous malformation (AVMs) and caused disruption of the lumen or lumen disorder. We show that excessive Sry-box 2 (Sox2) signaling was responsible for the EndMTs in cerebral AVMs. EC-specific suppression of Sox2 normalized endothelial differentiation and lumen formation, and improved the cerebral AVMs. Epigenetic studies showed that induction of Sox2 altered the cerebral-endothelial transcriptional landscape, and identified jumonji domain-containing protein 5 (JMJD5) as a direct target of Sox2. Sox2 interacted with JMJD5 to induce EndMTs in cerebral ECs. Furthermore, we utilized a high throughput system to identify the beta-adrenergic antagonist pronethalol as an inhibitor of Sox2 expression. Treatment with pronethalol stabilized endothelial differentiation and lumen formation, which limited the cerebral AVMs.
Overall design Discovery of histone modifications and Sox2 binding in cerebral endothelial cells (ECs) from Mgp knockout and wild type mice.
Contributor(s) Yao J, Wu X
Citation(s) 31232700
Submission date Apr 11, 2019
Last update date Aug 27, 2019
Contact name Yucheng Yao
Organization name UCLA
Street address 650 Charles Young Dr East, CHS A2-237
City Los Angeles
State/province CA
ZIP/Postal code 90095
Country USA
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (6)
GSM3718052 WT_Sox2_ChIPSeq
GSM3718053 KO_Sox2_ChIPSeq
GSM3718054 WT_H3K4me3_ChIPSeq
BioProject PRJNA532381
SRA SRP192021

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE129644_RAW.tar 222.3 Mb (http)(custom) TAR (of BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap