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Dinámica multidimensional temporal distinta en el desarrollo del cerebro humano

Matthew G Heffel^1,2, Jingtian Zhou^3,4,5, Yi Zhang¹

¹Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.

|October 9, 2024

Resumen

Este estudio revela cómo la metilación del ADN y la estructura de la cromatina cambian durante el desarrollo del cerebro. Estas ideas vinculan los factores de riesgo genéticos para la esquizofrenia con tipos específicos de células en el cerebro en desarrollo.

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Área de la Ciencia:

La neurociencia
La genómica
La epigenética

Sus antecedentes:

El hipocampo humano y la corteza prefrontal son vitales para la cognición.
El desarrollo molecular de estas regiones cerebrales no se comprende completamente.

Objetivo del estudio:

Investigar la reorganización epigenómica y tridimensional de la cromatina durante el desarrollo del cerebro.
Explorar los programas reguladores específicos del tipo de célula y su relación con los trastornos neuropsiquiátricos.

Principales métodos:

Se utilizaron más de 53.000 perfiles conjuntos de un solo núcleo de conformación de cromatina y metilación de ADN.
Se utiliza la secuenciación de un solo núcleo de metilo-3C (snm3C-seq).
Perfiles de una sola célula y imágenes multimodales de una sola molécula.

Principales resultados:

La remodelación de la metilación del ADN es temporalmente distinta de la dinámica de conformación de la cromatina.
Las interacciones de cromatina de corto alcance están enriquecidas con neuronas; las interacciones de largo alcance están enriquecidas con glial / no cerebral.
Se identificó una superposición entre las variantes de riesgo de esquizofrenia y las regiones reguladoras específicas del tipo de célula.

Conclusiones:

La multiomía 3D de una sola célula es poderosa para diseccionar los loci de riesgo neuropsiquiátrico.
Proporciona recursos multimodales para el estudio de la dinámica reguladora de genes en el desarrollo cerebral.
Revela patrones de interacción de cromatina distintos en las neuronas frente a las células gliales.