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Electroporation of Sliced Human Cortical Organoids for Studies of Gene Function
Published on: November 29, 2024
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Paisaje del transcriptoma y el epigenoma del desarrollo cortical humano modelado en organoides
Science (New York, N.Y.)
|December 15, 2018
Resumen
Los organoides cerebrales humanos modelan el desarrollo cortical cerebral temprano, revelando patrones de actividad de genes y potenciadores. Esta investigación identifica los posibles impulsores del trastorno del espectro autista en el desarrollo temprano del cerebro humano.
Área de la Ciencia:
- La neurociencia
- Biología del desarrollo
- La genética
Sus antecedentes:
- Estudiar el desarrollo temprano del cerebro humano y los trastornos neuropsiquiátricos es un desafío longitudinal.
- Los genes relacionados con los trastornos neuropsiquiátricos se expresan en el cerebro humano en desarrollo.
Objetivo del estudio:
- Modelar el desarrollo temprano de la corteza cerebral humana utilizando organoides derivados de células pluripotentes humanas.
- Identificar cambios moleculares y elementos reguladores cruciales para el desarrollo temprano del cerebro.
- Investigar el vínculo entre los elementos genéticos y el trastorno del espectro autista.
Principales métodos:
- Generación de organoides cerebrales a partir de células madre pluripotentes humanas.
- Análisis multiómico (actividad de genes y potenciadores) a través de puntos de tiempo de desarrollo.
- Análisis de la red para identificar patrones de corregulación de genes y potenciadores.
Principales resultados:
- Los organoides modelan con precisión los aspectos moleculares del desarrollo cortical cerebral hasta 16 semanas después de la concepción.
- Se observaron cambios significativos en la actividad del gen y del potenciador durante la transición de la célula madre al progenitor.
- Los módulos específicos de potenciador genético se asociaron con cambios evolutivos específicos del ser humano y variantes genéticas asociadas al autismo.
Conclusiones:
- Los organoides del cerebro humano proporcionan un modelo valioso para estudiar el desarrollo y la enfermedad temprana del cerebro humano.
- Los primeros patrones de actividad de genes y potenciadores son críticos para la formación del cerebro.
- Este modelo puede ayudar a descubrir elementos genéticos funcionales que contribuyen a trastornos neuropsiquiátricos como el autismo.
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