β-Catenin and Associated Proteins Regulate Lineage Differentiation in Ground State Mouse Embryonic Stem Cells
| Autor: | Fang Tao, Jay R. Unruh, Zhenrui Li, Sarah E. Smith, Michael P. Washburn, Da Zhang, John M. Perry, Deqing Hu, Laurence Florens, Pengxu Qian, Dai Tsuchiya, Chongbei Zhao, Xi C. He, Linheng Li, Jerry L. Workman, Jelly H.M. Soffers, Ying Zhang, Shiyuan Chen, Xin Gao, Meng Zhao, Aparna Venkatraman, Tari Parmely, Julia Zeitlinger |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Pluripotent Stem Cells
0301 basic medicine lineage differentiation Somatic cell Down-Regulation Biology germline Biochemistry Germline Article Mice 03 medical and health sciences 0302 clinical medicine Basic Helix-Loop-Helix Transcription Factors Genetics medicine Animals Cell Lineage ground state ESC ground state maintenance beta Catenin mouse embryogenesis naive pluripotency Wnt signaling pathway Cell Differentiation Mouse Embryonic Stem Cells Cell Biology Embryonic stem cell Wnt signaling Cell biology Chemically defined medium Germ Cells 030104 developmental biology medicine.anatomical_structure Epiblast Catenin embryonic structures 030217 neurology & neurosurgery Germ cell Protein Binding Transcription Factors Developmental Biology |
| Zdroj: | Stem Cell Reports |
| ISSN: | 2213-6711 |
| Popis: | Summary 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. Highlights • β-Catenin depletion irreversibly compromised lineage development of ground state ESCs • TCF3-independent role of β-catenin in determining lineage differentiation potential • E2F6, HP1γ, and HMGA2 are β-catenin interaction partners and co-bound to target genes • β-Catenin and protein partners fine-tune germline and neural development potential In this article, Tao and colleagues show that β-catenin functions beyond derepressing TCF3 targeted pluripotency network in ESCs. β-Catenin physically interacts with protein partners, including transcription factor and chromatin modulators. Together, they preserve the integrity of lineage differentiation of ground state ESCs by restraining and fine-tuning their germline and neural development potential. |
| Databáze: | OpenAIRE |
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