GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE120225 Query DataSets for GSE120225
Status Public on Aug 18, 2020
Title Channelopathy pathogenesis in a human neural cell model of Angelman Syndrome
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Angelman syndrome (AS) is a neurogenetic developmental disorder that results from the loss of E3 ubiquitin ligase UBE3A due to mutations in or deletions of the maternally inherited UBE3A allele. While mouse models of AS have implicated abnormal synaptic signaling and plasticity underlying behavioral dysfunction, how the loss of UBE3A contributes to hyperactivity of neuronal networks seen in AS patients remains unclear. Here, by utilizing human induced neurons and 3D cortical organoids derived from AS patient iPSCs and CRISPR-Cas9 mediated UBE3A KO hESCs, we uncovered a novel role of UBE3A in suppressing neuronal hyperexcitability via ubiquitin-mediated degradation of BK channels. More importantly, augmented BK channel activity in neurons manifested as increased intrinsic excitability of neurons and network level bursting and synchronization, which can be pharmacologically normalized by BK antagonists. Our study has illustrated the utility of modeling neurological diseases with human neural cells, and our results have provided new insights into underlying pathophysiological mechanisms and potential therapeutic strategy in Angelman syndrome.
Overall design 3 control vs 3 KO NGN2-induced neurons from H1 and H9 human embryonic stem cell lines
Contributor(s) Sun AX, Yuan Q, Fukuda M, Yu W, D'Agostino GA, Wang D, Tran H, Lokman H, Lim SW, Cook SA, Rackham OJ, Tan EK, Ng HH, Lim CT, Lim KL, Jiang Y, Je HS
Citation(s) 31857479
Submission date Sep 20, 2018
Last update date Aug 19, 2020
Contact name Giuseppe Alessandro D'Agostino
Organization name Lee Kong Chian School of Medicine - NTU
Lab Sarah Langley
Street address 11 Mandalay Road
City Singapore
State/province Singapore
ZIP/Postal code 308232
Country Singapore
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (6)
GSM3396294 E1_Ha_1: H9_WT_NGN2_1
GSM3396295 E2_C30_1: H9_KO_NGN2_2
GSM3396296 E3_Ha_2: H9_WT_NGN2_1
BioProject PRJNA492237
SRA SRP162220

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
GSE120225_RNAseq_ensembl92_all.counts.txt.gz 4.7 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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