β-catenin fluctuates in mouse ESCs and is essential for Nanog-mediated reprogramming of somatic cells to pluripotency
Mouse embryonic stem (ES) cells derived from the inner cell mass of the blastocyst can be maintained in culture, under pluripotent conditions, using Serum+LIF medium. However, it has been published that the minimal combination of two compounds (GSK3 and MEK inhibitors) can sustain mouse ES cell self...
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| Formato: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2014 |
| País: | España |
| Recursos: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/289619 |
| Acesso em linha: | http://hdl.handle.net/10803/289619 |
| Access Level: | acceso abierto |
| Palavra-chave: | Embryonic stem cells Fluctuations β-catenin Nanog Reprogramming Cèl·lules mare Fluctuacions Reprogramació 576 |
| Resumo: | Mouse embryonic stem (ES) cells derived from the inner cell mass of the blastocyst can be maintained in culture, under pluripotent conditions, using Serum+LIF medium. However, it has been published that the minimal combination of two compounds (GSK3 and MEK inhibitors) can sustain mouse ES cell self- renewal in absence of serum inhibiting ERK and Wnt/ β-catenin singaling pathways. Previous work of our laboratory has reported that periodic activation of the Wnt/β-catenin signalling pathway enhances reprogramming of somatic cells. Here we have demonstrated a dynamical interplay between β-catenin and Nanog in regulating both pluripotency and reprogramming. Specifically, fluctuations of Nanog affect β-catenin dynamics in serum+LIF, whereas, activation of the Wnt pathway, using Wnt3a or GSK3 inhibitors, causes β-catenin oscillations independent from Nanog. Moreover we have also proved that Nanog-mediate reprogramming depends on the indirect activation of the Wnt/β-catenin pathway. With our work we proposed a novel interaction between two parallel signalling pathways and provided a comprehensive mathematical model describing Nanog and β-catenin dynamics in mouse ES cells. |
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