β-Catenin and Associated Proteins Regulate Lineage Differentiation in Ground State Mouse Embryonic Stem Cells
Tao Fang, Jelly HM Soffers, Deqing Hu, Shiyuan Chen, Xin Gao, Ying Zhang, Chongbei Zhao, Sarah E. Smith, Jay R. Unruh, Da Zhang, Dai Tsuchiya, Aparna Venkatraman, Meng Zhao, Zhenrui Li, Pengxu Qian, Tari Parmely, Xi He, Michael P. Washburn, Laurence Florens, John M. Perry, Julia Zeitlinger, Jerry L. Workman, Linheng Li
Abstract
Mouse embryonic stem cells (ESCs) cultured in defined medium resemble the pre-implantation epiblast in the ground state, with full developmental capacity including the germline. β-Catenin is required to maintain ground state pluripotency in mouse ESCs, but its exact role is controversial. Here, we reveal a Tcf3-independent role of β-catenin in restraining germline and somatic lineage differentiation genes. We show that β-catenin binds target genes with E2F6 and forms a complex with E2F6 and HMGA2 or E2F6 and HP1γ. Our data indicate that these complexes help β-catenin restrain and fine-tune germ cell and neural developmental potential. Overall, our data reveal a previously unappreciated role of β-catenin in preserving lineage differentiation integrity in ground state ESCs.