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El control de la pluripotencia del estado fundamental por la regulación alélica de Nanog
Yusuke Miyanari1, Maria-Elena Torres-Padilla
1Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM U964, Université de Strasbourg, F-67404 Illkirch, Cité Universitaire de Strasbourg, France.
Nature
|February 14, 2012
Resumen
El gen Nanog se expresa desde un solo cromosoma en embriones tempranos, cambiando a ambos cromosomas para pluripotencia completa. Esta regulación alélica es crucial para el desarrollo adecuado y la reprogramación en embriones de mamíferos.
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:
- El establecimiento de la pluripotencia implica la reprogramación de todo el genoma y la activación de genes clave como Nanog y Oct4.
- Los mecanismos que regulan la expresión de Nanog y Oct4 in vivo durante el desarrollo preimplantacional de los mamíferos siguen sin estar claros.
Objetivo del estudio:
- Investigar los patrones de expresión alélica in vivo de Nanog y Oct4 durante el desarrollo temprano de los mamíferos.
- Para aclarar los mecanismos reguladores y el significado funcional de la expresión del alelo Nanog en el establecimiento de la pluripotencia.
Principales métodos:
- Análisis de la expresión alélica Nanog y Oct4 en embriones preimplantacionales y células madre embrionarias.
- Imágenes de células vivas de células Nanog reporteras para observar la conmutación alélica.
- Investigación de las vías reguladoras, incluida la señalización FGF / ERK y las modificaciones de la cromatina.
- Evaluación de blastocistos nanog-heterocigotos para los defectos del desarrollo.
Principales resultados:
- Nanog exhibe la expresión monoalélica en los primeros embriones, cambiando a la expresión bialélica durante la transición a la pluripotencia ingenua.
- Las células madre embrionarias muestran expresión monoalélica Nanog en LIF/suero pero expresión bialélica en condiciones 2i.
- La expresión alélica de Nanog está regulada por la señalización FGF / ERK e implica cambios en la cromatina, independientemente de la metilación del ADN.
- Los blastocistos nanog-heterocigotos muestran un deterioro en el desarrollo de la masa celular interna y un retraso en la formación del endodermo primitivo.
Conclusiones:
- La expresión alélica de Nanog es un mecanismo regulador crítico que controla la dosis del factor de pluripotencia durante el desarrollo de los mamíferos.
- La regulación estricta de la dosis de Nanog a nivel cromosómico es esencial para la adquisición de pluripotencia en el estado fundamental.
- Este estudio revela un papel inesperado para la expresión alélica en la regulación de la reprogramación y la pluripotencia in vivo.
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