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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
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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.
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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.
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Citation(s) |
38354738 |
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Submission date |
Oct 23, 2023 |
Last update date |
Apr 19, 2024 |
Contact name |
Nathan J. Palpant |
Organization name |
University of Queensland
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Street address |
306 Carmody Road
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City |
Birsbane |
State/province |
QLD |
ZIP/Postal code |
4067 |
Country |
Australia |
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Platforms (1) |
GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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Samples (15)
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GSM7855197 |
WTC-11, 1CHIR+tranilast, rep1, RNAseq |
GSM7855198 |
WTC-11, 1CHIR+tranilast, rep2, RNAseq |
GSM7855199 |
WTC-11, 1CHIR+tranilast, rep3, RNAseq |
GSM7855200 |
WTC-11, 3CHIR, rep1, RNAseq |
GSM7855201 |
WTC-11, 3CHIR, rep2, RNAseq |
GSM7855202 |
WTC-11, 3CHIR, rep3, RNAseq |
GSM7855203 |
WTC-11, 3CHIR+tranilast, rep1, RNAseq |
GSM7855204 |
WTC-11, 3CHIR+tranilast, rep2, RNAseq |
GSM7855205 |
WTC-11, 3CHIR+tranilast, rep3, RNAseq |
GSM7855206 |
WTC-11, tranilast, rep1, RNAseq |
GSM7855207 |
WTC-11, tranilast, rep2, RNAseq |
GSM7855208 |
WTC-11, tranilast, rep3, RNAseq |
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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 |
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Relations |
BioProject |
PRJNA1031238 |
Supplementary file |
Size |
Download |
File type/resource |
GSE246079_RAW.tar |
2.9 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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