GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE115421 Query DataSets for GSE115421
Status Public on Jan 11, 2019
Title Patient adipose stem cell-derived adipocytes reveal genetic variation that predicts anti-diabetic drug response
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Thiazolidinedione drugs (TZDs) target the transcriptional activity of PPARg to reverse insulin resistance in type 2 diabetes, but side effects limit their clinical use. Here, using human adipose stem cell-derived adipocytes, we demonstrate that single-nucleotide polymorphisms (SNPs) were enriched at sites of patient-specific PPARg binding, which correlated with the individual-specific effects of TZD rosiglitazone (rosi) on gene expression. Rosi induction of ABCA1, which regulates cholesterol metabolism, was dependent upon SNP rs4743771, which modulated PPARg binding by influencing the genomic occupancy of its cooperating factor NFIA. Conversion of rs4743771 from the inactive SNP allele to the active one by CRISPR/Cas9-mediated editing rescued PPARg binding as well as rosi-induction of ABCA1 expression. Moreover, rs4743771 is a major determinant of undesired serum cholesterol increases in rosi-treated diabetics. These data highlight human genetic variation that impacts PPARg genomic occupancy and patient responses to antidiabetic drugs, with implications for developing personalized therapies for metabolic disorders
Overall design hACSs derived from obstity patient were differentiated into adipocytes; then treated with rosiglitazone
Web link
Contributor(s) Hu W, Jiang C
Citation(s) 30639037
Submission date Jun 06, 2018
Last update date Nov 20, 2020
Contact name Chunjie Jiang
Phone 2153164211
Organization name University of Pennsylvania
Department Institute for Diabetes, Obesity, and Metabolism
Lab Mitchell A. Lazar
Street address 3400 Civic Center Boulevard
City Philadelphia
State/province PA
ZIP/Postal code 19104
Country USA
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (62)
GSM3177920 P1_Adipocytes_DMSO_1
GSM3177921 P1_Adipocytes_DMSO_2
GSM3177922 P1_Adipocytes_DMSO_3
BioProject PRJNA474921
SRA SRP149925

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
GSE115421_ExpressionProfile.txt.gz 2.3 Mb (ftp)(http) TXT
GSE115421_RAW.tar 1000.3 Mb (http)(custom) TAR (of BIGWIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file

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