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Series GSE253606 Query DataSets for GSE253606
Status Public on Jan 25, 2024
Title 6 h FGF4 stimulation of Fgf4-mutant mESCs [bulkRNA-seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Cell differentiation results from coordinated changes in gene transcription in response to combinations of signals. FGF, Wnt, and mTOR signals regulate the differentiation of pluripotent mammalian cells towards embryonic and extraembryonic lineages, but how these signals cooperate with general transcriptional regulators is not fully resolved. Here, we report a genome-wide CRISPR screen that reveals both signaling components and general transcriptional regulators for differentiation-associated gene expression in mESCs. Focusing on the Mediator subunit Med12 as one of the strongest hits in the screen, we show that it regulates gene expression in parallel to FGF and mTOR signals. Loss of Med12 is compatible with differentiation along both the embryonic epiblast and the extraembryonic primitive endoderm lineage, but pluripotency transitions are slowed down, and the transcriptional separation between epiblast and primitive endoderm identities is enhanced in Med12-mutant cells. These cellular phenotypes correlate with reduced biological noise upon loss of Med12. These findings suggest that Med12 regulates cellular plasticity through the priming of transcriptional changes during differentiation, thereby modulating the effects of a broad range of signals.
 
Overall design To investigate FGF4 target genes in mESCs, we used a Fgf4-mutant line and stimulated cells for 6h with different concentrations of FGF4.
 
Contributor(s) Fernkorn M, Schröter C
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Submission date Jan 18, 2024
Last update date Jan 25, 2024
Contact name Max Fernkorn
E-mail(s) m.fernkorn@lacdr.leidenuniv.nl
Organization name University Leiden
Department Leiden Academic Centre for Drug Research (LACDR)
Lab Drukker
Street address Einsteinweg 55
City Leiden
ZIP/Postal code 2333 CC
Country Germany
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (8)
GSM8024035 mESCs, unstimulated
GSM8024036 mESCs, stimulated, 6h 0.625 ng/ml FGF4
GSM8024037 mESCs, stimulated, 6h 1.25 ng/ml FGF4
This SubSeries is part of SuperSeries:
GSE253609 Med12 cooperates with multiple differentiation signals to enhance embryonic stem cell plasticity
Relations
BioProject PRJNA1066347

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
GSE253606_All_Probes_Raw_Counts.txt.gz 1.6 Mb (ftp)(http) TXT
GSE253606_All_Probes_TPMs.txt.gz 2.7 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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