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Series GSE228663 Query DataSets for GSE228663
Status Public on Oct 13, 2023
Title Functional interrogation of twenty Type 2 Diabetes-associated genes using isogenic hESC-derived β-like cells [ATAC-Seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Genetic studies have identified numerous loci associated with type 2 diabetes (T2D), but the functional role of many loci has remained unexplored. In this study, we engineered isogenic knockout human embryonic stem cell (hESC) lines for 20 genes associated with T2D risk. We systematically examined β-cell differentiation, insulin production and secretion, and survival. We performed RNA-seq and ATAC-seq on hESC-β cells from each knockout line. Analyses of T2D GWAS signals overlapping with HNF4A-dependent ATAC peaks identified a specific SNP as a likely causal variant. In addition, we performed integrative association analyses and identified four genes (CP, RNASE1, PCSK1N and GSTA2) associated with insulin production, and two genes (TAGLN3 and DHRS2) associated with sensitivity to lipotoxicity. Finally, we leveraged deep ATAC-seq read coverage to assess allele-specific imbalance at variants heterozygous in the parental hESC line, to identify a single likely functional variant at each of 23 T2D GWAS signals.
 
Overall design Comparative gene expression profiling analysis of RNA-seq data for beta-like cells derived from WT hESC and its KO derivatives with knockout of 20 T2D associated genes
 
Contributor(s) Xue D, Narisu N, Taylor DL, Zhang M, Grenko C, Yan T, Sinha N, Erdos MR, Bonnycastle LL, Chen S, Collins FS
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Submission date Mar 31, 2023
Last update date Oct 13, 2023
Contact name Shuibing Chen
E-mail(s) shuibing.chen@gmail.com
Phone 2127465431
Organization name Weill Cornell Medical College
Department Surgery
Street address A 827B, 1300 York Ave
City New York
State/province NY
ZIP/Postal code 10065
Country USA
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (67)
GSM7134672 ABCC8_C1 [ATAC-Seq]
GSM7134673 ABCC8_C2 [ATAC-Seq]
GSM7134674 ABCC8_C3 [ATAC-Seq]
This SubSeries is part of SuperSeries:
GSE228665 Functional interrogation of twenty Type 2 Diabetes-associated genes using isogenic hESC-derived β-like cells
Relations
BioProject PRJNA950979

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

Supplementary file Size Download File type/resource
GSE228663_ATAC_raw_read_counts.tsv.gz 19.8 Mb (ftp)(http) TSV
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Raw data are available in SRA
Processed data are available on Series record

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