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La multiomía espacial revela compartimentos nucleares específicos para el tipo de célula

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Resumen
Este resumen es generado por máquina.

Este estudio introduce la secuencia de ADN de dos capas FISH+ para mapear los loci genómicos, el transcriptoma y las estructuras nucleares en células individuales. Revela la organización de la cromatina específica del tipo celular y la regulación génica en el cerebelo del ratón.

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Área de la Ciencia:

  • Biología celular
  • La genómica
  • La epigenética

Sus antecedentes:

  • El núcleo de los mamíferos contiene diversas estructuras subnucleares específicas del tipo de célula que influyen en la regulación genética y la organización del genoma.
  • Comprender estas estructuras requiere mapear sus componentes moleculares, asociaciones genómicas y efectos de transcripción en células individuales dentro de tejidos complejos.

Objetivo del estudio:

  • Desarrollar y aplicar un nuevo método multiómico de alta resolución para el mapeo simultáneo de los loci genómicos, el transcriptoma naciente y las estructuras subnucleares en células individuales.
  • Investigar la organización de la cromatina específica del tipo celular, la regulación génica y el papel de las estructuras subnucleares en tejidos complejos.

Principales métodos:

  • Desarrollo de la secuencia de ADN de dos capas FISH+ para el mapeo simultáneo de 100 049 loci genómicos, el transcriptoma naciente de 17 856 genes y las estructuras subnucleares en células individuales.
  • Aplicación del método a conjuntos de datos multiómicos del cerebelo de ratones adultos.
  • Análisis de datos de perfiles de cromatina basados en imágenes a escalas genómicas desde 100-200 kilobases hasta ~ 1 megabase.

Principales resultados:

  • Las regiones de cromatina represivas exhiben una mayor variabilidad de tipo celular que las regiones activas en todo el genoma.
  • Los focos de ARN polimerasa II se asocian con genes largos específicos del tipo celular, distintos de las manchas nucleares.
  • La heterocromatina específica del tipo celular (H3K27me3, H4K20me3) se enriquece en genes/grupos, influyendo en el posicionamiento cromosómico y las interacciones en las neuronas y las células gliales.

Conclusiones:

  • La secuencia de ADN de dos capas FISH+ proporciona una vista multicelular de alta resolución de las estructuras subnucleares y sus asociaciones genómicas.
  • Los hallazgos ofrecen información sobre los efectos de las estructuras subnucleares en la regulación génica y la organización tridimensional del genoma dentro de tejidos complejos.