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Series GSE99202 Query DataSets for GSE99202
Status Public on Jan 08, 2018
Title YAP Repression of the WNT3 Gene Controls hESC Differentiation Along the Cardiac Mesoderm Lineage
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary In hESCs, Wnt3/β-catenin activity is low and Activin/SMAD signaling ensures NANOG expression to sustain pluripotency. In response to exogenous Wnt3 effectors, Activin/SMADs switch to cooperate with β-catenin and induce mesendodermal differentiation genes. We show here that the HIPPO effector YAP binds to the WNT3 gene enhancer and prevents the gene from being induced by Activin in proliferating hESCs. In the absence of YAP, Activin signaling is sufficient to induce expression of the endogenous Wnt3 cytokine, which stabilizes β-catenin and selectively activates genes required for cardiac mesoderm (ME) formation. Interestingly, Activin-stimulated YAP-knockout hESCs strongly express β-catenin-dependent cardiac mesoderm markers (BAF60c and HAND1), but unlike WT hESCs, fail to express cardiac inhibitor genes (CDX2, MSX1). Accordingly, YAP-/- cells treated with Activin alone can differentiate efficiently to beating cardiomyocytes in culture, bypassing the need for sequential treatment with exogenous Wnt ligand and Wnt inhibitors. Similarly, Activin in combination with small-molecule YAP inhibitors generates beating cardiomyocytes from wild-type hESCs following a one- step protocol. Our findings highlight an unanticipated role of YAP as an upstream regulator of WNT3 to maintain hESC pluripotency in the presence of Activin, and uncover a direct route for the development of human embryonic cardiac mesoderm.
 
Overall design We performed a set of sequencing experiments to identify the role of YAP in hESCs and whether YAP influences the activity of the Activin and Wnt signaling pathways during the mesoderm differentiation. We performed transcriptional profile of WT and YAP-KO cells under different Wnt or Activin treatments and performed ChIP-seq analysis of the Wnt and Activin effectors beta-catenin and Smad2,3. In parallel we also mapped the binding of the YAP protein together with TEAD4 DNA-binding protein in hESCs. As a read-out of transcriptional activity under the different treatments we performed ChIP-seq of the active elongation mark CTD-Ser7P RNAPII.
 
Contributor(s) Estaras C, Huang L
Citation(s) 29269485, 30449705
Submission date May 23, 2017
Last update date May 15, 2019
Contact name Ling Huang
E-mail(s) lhuang@salk.edu
Organization name The Salk Institute
Department IGC
Street address 10010 N Torrey Pines Rd
City La Jolla, San Diego
State/province CA
ZIP/Postal code 92037
Country USA
 
Platforms (2)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (70)
GSM2635678 ChIPSeq_Beta_WT_Act
GSM2635679 ChIPSeq_Beta_YAP-_Act
GSM2635680 ChIPSeq_Input_WT_Act
Relations
BioProject PRJNA387555
SRA SRP107845

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
GSE99202_RAW.tar 18.3 Mb (http)(custom) TAR (of BED)
GSE99202_RNASeq1_count.xlsx.gz 2.2 Mb (ftp)(http) XLSX
GSE99202_RNASeq2_count.xlsx.gz 4.5 Mb (ftp)(http) XLSX
GSE99202_RNASeq3_count.xlsx 2.9 Mb (ftp)(http) XLSX
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file

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