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Función del regulador epigenético a través de la gastrulación del ratón

Stefanie Grosswendt1, Helene Kretzmer1, Zachary D Smith2,3,4

  • 1Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.

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|July 31, 2020
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Resumen
Este resumen es generado por máquina.

Este estudio revela que el complejo represivo Polycomb 2 (PRC2) juega un papel clave en la restricción del destino de la línea germinal durante el desarrollo temprano del ratón. Los fenotipos mutantes PRC aparecen antes de la gastrulación, ofreciendo nuevas ideas sobre la determinación del destino celular.

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Área de la Ciencia:

  • Biología del desarrollo
  • La epigenética
  • La genómica

Sus antecedentes:

  • La determinación del destino celular durante el desarrollo se basa en factores de transcripción y maquinaria epigenética.
  • Comprender los roles precisos del desarrollo de estos reguladores es un desafío debido a fenotipos mutantes complejos.
  • La secuenciación de ARN unicelular ha avanzado en el estudio del desarrollo embrionario temprano.

Objetivo del estudio:

  • Investigar las funciones de los reguladores esenciales del desarrollo en la embriogénesis temprana del ratón.
  • Analizar las funciones de los complejos represivos de Polycomb (PRC1 y PRC2) en la restricción del destino celular.
  • Desarrollar una plataforma para el análisis simultáneo de múltiples embriones de ratón mutantes.

Principales métodos:

  • Utilizó una perturbación zigótica combinada y una plataforma de secuenciación de ARN de una sola célula.
  • Se analizaron simultáneamente varios embriones de ratón mutantes para obtener datos morfológicos y de transcripción.
  • Centrado en diez reguladores esenciales del desarrollo, incluidos los componentes PRC1 y PRC2.

Principales resultados:

  • Se identificó una cooperación sustancial entre PRC1 y PRC2, con PRC2 mostrando un papel dominante en la restricción de la línea germinal.
  • Se observó que los fenotipos mutantes de la RPC se manifiestan antes de la gastrulación, después de cambios epigenéticos y transcripcionales tempranos.
  • Generó información morfológica y transcripcional robusta en diez reguladores esenciales.

Conclusiones:

  • PRC2 es crítico para restringir el destino de la línea germinal en el desarrollo temprano del ratón.
  • Los efectos del desarrollo mediados por la PRC preceden a la gastrulación.
  • El marco experimental desarrollado permite el análisis cuantitativo de la aparición de la diversidad celular a partir de una sola célula.