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Series GSE189860 Query DataSets for GSE189860
Status Public on Dec 01, 2021
Title Transcriptomic and Epigenomic Profiles of CIC-knockout and IDH1 mutant cells [WGBS]
Organism Homo sapiens
Experiment type Methylation profiling by high throughput sequencing
Summary Capicua (CIC)’s transcriptional repressor function is implicated in neurodevelopment and in oligodendroglioma (ODG) aetiology. However, CIC’s role in these contexts remains obscure, primarily from our currently limited knowledge regarding its biological functions. Moreover, CIC mutations in ODG invariably co-occur with a neomorphic IDH1/2 mutation, yet the functional relationship between these two genetic events is unknown. Here, we analysed models derived from an E6/E7/hTERT-immortalized (i.e. p53- and RB-deficient) normal human astrocyte cell line. To examine the consequences of CIC loss, we compared transcriptomic and epigenomic profiles between CIC wildtype and knockout cell lines, with and without mutant IDH1 expression. Our analyses revealed dysregulation of neurodevelopmental genes in association with CIC loss. CIC ChIP-seq was also performed to expand upon the currently limited ensemble of known CIC target genes. Among the newly identified direct CIC target genes were EPHA2 and ID1, whose functions are linked to neurodevelopment and the tumourigenicity of in vivo glioma tumour models. NFIA, a known mediator of gliogenesis, was discovered to be uniquely overexpressed in double mutant cells (CIC-knockout + IDH1-mutant). These results identify neurodevelopment and specific genes within this context as candidate targets through which CIC alterations may contribute to the progression of IDH-mutant gliomas.
Overall design Whole-genome bisulfite sequencing performed in immortalized normal human astrocytes stably expressing IDH1-WT or IDH1-R132H, and in matched CIC knockout lines (two independent replicates each).
Contributor(s) Lee SD, Song J, LeBlanc VG, Marra MA
Citation(s) 34767259
Submission date Nov 30, 2021
Last update date Dec 03, 2021
Contact name Marco A Marra
Organization name Canada's Michael Smith Genome Sciences Centre
Street address 675 W 10th Ave, 7th Floor
City Vancouver
State/province BC
ZIP/Postal code V5Z 1L3
Country Canada
Platforms (1)
GPL20795 HiSeq X Ten (Homo sapiens)
Samples (12)
GSM5708739 CIC-WT (IDH1-WT) WGBS rep 1
GSM5708740 CIC-WT (IDH1-WT) WGBS rep 2
GSM5708741 CIC-KO1 (IDH1-WT) WGBS rep 1
This SubSeries is part of SuperSeries:
GSE189861 Transcriptomic and Epigenomic Profiles of CIC-knockout and IDH1 mutant cells
BioProject PRJNA784800
SRA SRP348645

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Supplementary file Size Download File type/resource
GSE189860_RAW.tar 2.7 Gb (http)(custom) TAR (of BED)
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Raw data are available in SRA
Processed data provided as supplementary file

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