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La ronina es esencial para la embriogénesis y la pluripotencia de las células madre embrionarias de ratón
Marion Dejosez1, Joshua S Krumenacker, Laura Jo Zitur
1Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA.
Cell
|July 1, 2008
Resumen
La ronina, un nuevo factor de pluripotencia, es esencial para el desarrollo embrionario temprano y la auto-renovación de las células madre embrionarias (CEM). Se une a HCF-1, lo que sugiere un papel epigenético en el mantenimiento de la pluripotencia.
Área de la Ciencia:
- Biología del desarrollo Biología del desarrollo.
- La epigenética es la epigenética.
- Biología de las células madre Biología de las células madre
Sus antecedentes:
- La pluripotencia permite a las células diferenciarse en todos los tipos de tejidos.
- Los mecanismos moleculares que gobiernan la pluripotencia no se comprenden completamente.
- La identificación de nuevos factores involucrados en la pluripotencia es crucial para el desarrollo y la medicina regenerativa.
Objetivo del estudio:
- Identificar y caracterizar un nuevo candidato al factor de pluripotencia.
- Investigar el papel de este factor en la embriogénesis temprana y la auto-renovación de las células madre embrionarias (CEM).
- Para dilucidar el mecanismo molecular por el cual este factor regula la expresión génica.
Principales métodos:
- Describió un nuevo candidato al factor de pluripotencia, Ronin, que posee un dominio THAP.
- Investigó la expresión de Ronin durante el desarrollo embrionario murino.
- Utilizó knockout condicional y expresión forzada en ratones y ESC.
- Realizó co-inmunoprecipitación para identificar socios vinculantes, incluido el HCF-1.
Principales resultados:
- La ronina se expresa en el desarrollo murino temprano y su deficiencia causa letalidad de periimplantación y defectos de masa celular interna.
- El nocaut condicional de Ronin detiene la proliferación del ESC, mientras que su expresión forzada promueve la auto-renovación del ESC sin diferenciación.
- Ronin rescata parcialmente los efectos de knockdown de Oct4 en los CES.
- La ronina se une directamente al regulador de la transcripción HCF-1.
Conclusiones:
- La ronina es un factor esencial para la embriogénesis y la pluripotencia ESC.
- La interacción de la ronina con el HCF-1 sugiere un papel en la represión epigenética del gen en las células pluripotentes.
- Este descubrimiento proporciona nuevos conocimientos sobre la regulación molecular de la pluripotencia y el desarrollo temprano.
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