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Series GSE246079 Query DataSets for GSE246079
Status Public on Jan 19, 2024
Title Dose escalation of Wnt stimulation during the exit from pluripotency identifies tranilast as a small molecule regulator of cardiac mesoderm differentiation (RNA-Seq)
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Wnt signalling is a critical determinant of cell lineage development. This study used Wnt dose-dependent induction programs to gain insights into molecular regulation of stem cell differentiation. We performed single cell RNA-sequencing of cells responding to a dose-escalation protocol with Wnt agonist CHIR-99021 during the exit from pluripotency to identify cell types and genetic activity driven by Wnt stimulation. Results of activated gene sets and cell types were then used to build a multiple regression model that predicts the efficiency of cardiomyocyte differentiation. Cross-referencing Wnt-associated gene expression profiles to the Connectivity Map database, we identified a novel property of the small molecule drug, tranilast. We found that tranilast synergistically activates Wnt signalling to promote cardiac lineage differentiation which we validate in vitro and in vivo. Our study provides an integrated workflow that links experimental datasets, prediction models and small molecule databases to identify novel drug-like compounds that control cell differentiation.
 
Overall design WTC-11 cells differentiated under different conditions were harvested for bulk RNA-seq on day 2. We then performed differential gene expression and gene ontology analysis to understand the mechanisms of tranilast on the regulation of cardiomyocyte differentiation.
 
Citation(s) 38354738
Submission date Oct 23, 2023
Last update date Apr 19, 2024
Contact name Nathan J. Palpant
Organization name University of Queensland
Street address 306 Carmody Road
City Birsbane
State/province QLD
ZIP/Postal code 4067
Country Australia
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (15)
GSM7855194 WTC-11, 1CHIR, rep1, RNAseq
GSM7855195 WTC-11, 1CHIR, rep2, RNAseq
GSM7855196 WTC-11, 1CHIR, rep3, RNAseq
This SubSeries is part of SuperSeries:
GSE246081 Dose escalation of Wnt stimulation during the exit from pluripotency identifies tranilast as a small molecule regulator of cardiac mesoderm differentiation
Relations
BioProject PRJNA1031238

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
GSE246079_RAW.tar 2.9 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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