Investigating the role of transcription factor Nkx1-2 in mouse embryonic stem cell pluripotency, self-renewal and differentiation
Mouse embryonic stem cells (ESCs) require extracellular signals to induce the expression of intrinsic core pluripotency factors: Oct4, Sox2 and Nanog, known as the OSN triad. Notably, the Wnt/β-catenin pathway has been shown to be important for controlling the expression of transcription factors tha...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/668122 |
| Acceso en línea: | http://hdl.handle.net/10803/668122 |
| Access Level: | acceso abierto |
| Palabra clave: | Stem cell Pluripotency Transcription factor Self-renewal Differentiation Mouse Development Inner cell mass Early embryo Chimera 576 |
| Sumario: | Mouse embryonic stem cells (ESCs) require extracellular signals to induce the expression of intrinsic core pluripotency factors: Oct4, Sox2 and Nanog, known as the OSN triad. Notably, the Wnt/β-catenin pathway has been shown to be important for controlling the expression of transcription factors that orchestrate the characteristic ESC gene expression programme. It remains unclear, however, the exact mechanisms by which the Wnt pathway (via tcf3) contributes to enhance the maintenance of ESCs in a naïve state. Furthermore, little is known of the identity of Wnt-dependent downstream targets that elegantly regulate this ESC state. To identify these Wnt- dependent important transcription factors (TFs) or master regulators (MRs), we used a reverse engineering approach that allowed us to identify several TFs with unknown function in ESCs. The work in this thesis is focused on investigating the function of Nkx1-2 in controlling naïve pluripotency, and we propose it as a novel TF as it had never been described before. Here, we discovered that Nkx1-2 has dual functions in ESC biology. In fact, Nkx1-2 can delay ESC differentiation upon LIF withdrawal and its deletion leads to abnormal pluripotency-specific protein expression. Also, Nkx1-2 is important for ESC differentiation and cell-fate specification in the early mouse embryo development. Overall, this work reveals a novel role for Nkx1-2 in ESC pluripotency and differentiation. |
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