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Jmjd3 inhibe la reprogramación mediante la regulación hacia arriba de la expresión de INK4a/Arf y la orientación de
Wei Zhao1, Qingtian Li, Stephen Ayers
1Center for Inflammation and Epigenetics, The Methodist Hospital Research Institute, Houston, TX 77030, USA.
Cell
|March 5, 2013
Resumen
Jmjd3 regula negativamente la reprogramación celular en las células madre pluripotentes inducidas (iPSC). Su ausencia mejora la generación de iPSC, mientras que su presencia la inhibe, revelando un nuevo eje regulador Jmjd3-PHF20.
Área de la Ciencia:
- La epigenética es la epigenética.
- Biología de las células madre Biología de las células madre
- Biología Molecular Biología Molecular
Sus antecedentes:
- La reprogramación de las células somáticas para generar células madre pluripotentes inducidas (iPSC) implica alteraciones epigenéticas significativas.
- Los roles y mecanismos precisos de los reguladores epigenéticos en este proceso no están completamente aclarados.
Objetivo del estudio:
- Identificar y caracterizar nuevos factores epigenéticos que regulan la reprogramación de las células somáticas.
- Aclarar los mecanismos moleculares por los cuales Jmjd3 influye en la generación de iPSCs.
Principales métodos:
- Generación y análisis de fibroblastos embrionarios de ratón de tipo salvaje y con deficiencia de Jmjd3.
- Evaluación de la formación de colonias iPSC sobre la expresión ectópica Jmjd3.
- Investigación de la interacción de Jmjd3 con PHF20 y Trim26, incluyendo ensayos de ubiquitinación.
- Análisis de los MEF con deficiencia de PHF20 en experimentos de reprogramación.
Principales resultados:
- Jmjd3 actúa como un potente regulador negativo de la reprogramación; los MEF deficientes en Jmjd3 producen más colonias iPSC.
- Jmjd3 inhibe la reprogramación a través de mecanismos dependientes y independientes de la histona desmetilasa.
- El eje Jmjd3-PHF20 es crítico, ya que la deficiencia de PHF20 impide la generación de iPSC incluso cuando Jmjd3 es derribado.
Conclusiones:
- Jmjd3 es un regulador negativo no reconocido previamente de la reprogramación celular.
- El eje Jmjd3-PHF20 juega un papel crucial en el control de la eficiencia de la generación iPSC.
- Este estudio proporciona nuevos conocimientos moleculares sobre la regulación epigenética de la reprogramación.
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