PLX045510

GSE108620: -catenin associated protein complex maintains ground state mouse embryonic stem cell by regulating lineage development

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

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 -catenin is known to be crucial for naive pluripotency of ES cells, the mechanism is not fully understood. Here we showed that -catenin interacted with a repressive protein complex to maintain the ground state of ES cells by fine-tuning their lineage development potential. Absence of -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, -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 -catenin-deficient phenotype of ES cells. Mechanistically, -catenin formed a novel biochemical complex with E2F6, HP1 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 -catenin maintained ground state ES cells by orchestrating their development plasticity through a repressive protein complex with E2F6, HP1 and HMGA2. SOURCE: Shiyuan,(Cynthia),Chen (shc@stowers.org) - Stowers Institute for Medical Research