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Series GSE108620 Query DataSets for GSE108620
Status Public on Aug 20, 2020
Title β-catenin associated protein complex maintains ground state mouse embryonic stem cell by regulating lineage development
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Mouse embryonic stem (ES) cells cultured in defined medium with MEK and GSK3 inhibitors (2i) resemble the pre-implantation epiblast in the ground state, with full development capacity including the somatic lineages and the germline. Although β-catenin is known to be crucial for naive pluripotency of ES cells, the mechanism is not fully understood. Here we showed that β-catenin interacted with a repressive protein complex to maintain the ground state of ES cells by fine-tuning their lineage development potential. Absence of β-catenin impaired ES cell self-renewal without affecting the core self-renewal circuitry of Oct4, Sox2 and Nanog as well as other pluripotency factors. However, β-catenin-deficient cells showed a primed state transcriptional signature with perturbed expression of germline and neuronal lineage genes. Knockdown of Tcf7l1, the repressor in canonical Wnt signaling pathway, did not completely rescue the β-catenin-deficient phenotype of ES cells. Mechanistically, β-catenin formed a novel biochemical complex with E2F6, HP1γ and HMGA2 to restrain ES cells from differentiation by co-occupying the promoters of germline and neuronal lineage regulators independent of TCF7L1. Overall, out work showed that β-catenin maintained ground state ES cells by orchestrating their development plasticity through a repressive protein complex with E2F6, HP1γ and HMGA2.
 
Overall design Analyzing developmental genes regulated by β-catenin and associated protein complex
 
Contributor(s) Tao F, Li L
Citation(s) 32822591, 36595937
Submission date Dec 28, 2017
Last update date Jan 11, 2023
Contact name Shiyuan (Cynthia) Chen
E-mail(s) shc@stowers.org
Organization name Stowers Institute for Medical Research
Department Computational Biology
Street address 1000 E 50th St
City Kansas City
State/province MO
ZIP/Postal code 64110
Country USA
 
Platforms (2)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (50)
GSM2907067 Cov_Flag_ctnnb1
GSM2907068 V6.5_2i_shGFP_input
GSM2907069 V6.5_2i_shGFP_TCF3_rep1
Relations
BioProject PRJNA427829
SRA SRP130920

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
GSE108620_Fang_bcat_FPKM.csv.gz 566.5 Kb (ftp)(http) CSV
GSE108620_RAW.tar 4.9 Gb (http)(custom) TAR (of BW)
GSE108620_RSEM_TPM_table_2742.csv.gz 744.0 Kb (ftp)(http) CSV
GSE108620_RSEM_TPM_table_2804.csv.gz 743.2 Kb (ftp)(http) CSV
GSE108620_RSEM_TPM_table_2984.csv.gz 832.5 Kb (ftp)(http) CSV
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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