The Role of SMYD2 during human embryonic stem cells differentiation
Embryonic stem (ES) cells are able to differentiate into any cell type, a property called pluripotency, and have unlimited potential for self-renewal. Although the molecular mechanisms responsible for maintaining self-renewal and pluripotency in ES cells are not well known, recent studies have demon...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2013 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/128681 |
| Acceso en línea: | http://hdl.handle.net/10803/128681 |
| Access Level: | acceso abierto |
| Palabra clave: | SMYD2 Differentiation Development Stem cells Methyltransferase Zebrafish 576 |
| Sumario: | Embryonic stem (ES) cells are able to differentiate into any cell type, a property called pluripotency, and have unlimited potential for self-renewal. Although the molecular mechanisms responsible for maintaining self-renewal and pluripotency in ES cells are not well known, recent studies have demonstrated the importance of epigenetic mechanisms in maintaining these processes. Histone modifying enzymes play decisive roles in differentiation and development. This study describes that SMYD2 (SET and MYND domain containing protein 2), a histone lysine methyltransferase, is induced during human ES cells differentiation and it is preferentially expressed in somatic cells versus pluripotent cells. Gain and loss-of-function experiments have shown that knockdown of SMYD2 in human ES cells promotes the induction of endodermal markers during differentiation, while overexpression has opposite effects. In vivo experiments in zebrafish revealed that knockdown of smyd2a (a homologue gene of human SMYD2) causes developmental delays and aberrant tail formation. The phenotype of smyd2a-morphant embryos correlates with a low expression of ntl and over induction Nodal-related genes during gastrulation. Finally, SMYD2 is shown to stimulate the activation of BMP signaling pathway and promotes the induction of BMP2-target genes in human ES cells. Overall, these findings suggest that SMYD2 plays a critical role at early stages during development and in human ES cells differentiation. |
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