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Combining Human Organoids and Organ-on-a-Chip Technology to Model Intestinal Region-Specific Functionality
Published on: May 5, 2022
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Autoorganización y ruptura de simetría en el desarrollo organoide intestinal
Denise Serra1,2, Urs Mayr1,2, Andrea Boni1,3
1Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
Nature
|April 26, 2019
Resumen
Los organoides intestinales se desarrollan a través de un proceso de regeneración impulsado por la activación de YAP1. Esta actividad génica transitoria desencadena la diferenciación celular, lo que lleva a la formación de estructuras complejas y asimétricas a partir de células individuales.
Área de la Ciencia:
- Biología de las células madre
- Biología del desarrollo
- Tecnología de organoides
Sus antecedentes:
- Los organoides intestinales imitan la estructura del intestino y los tipos de células.
- La autoorganización de las células madre forma tejidos complejos.
- La ruptura de simetría inicia la diferenciación en células especializadas como las células de Paneth.
Objetivo del estudio:
- Caracterizar el desarrollo unicelular de los organoides intestinales.
- Para comprender los mecanismos moleculares que impulsan la formación temprana de organoides.
- Investigar el papel de YAP1 en la ruptura de simetría y la diferenciación celular.
Principales métodos:
- Genómica cuantitativa de una sola célula.
- Técnicas de imágenes de alta resolución.
- Análisis de la expresión génica y el comportamiento celular.
Principales resultados:
- El desarrollo del organoide sigue un proceso de regeneración.
- La activación transitoria de YAP1 impulsa el desarrollo.
- La variabilidad de célula a célula en YAP1 inicia la señalización de Notch y DLL1.
- Este proceso conduce a la primera formación de células de Paneth y a la ruptura de la simetría.
Conclusiones:
- Las células individuales pueden autoorganizarse en estructuras complejas.
- La señalización mediada por YAP1 es crucial para iniciar el desarrollo asimétrico.
- La autoorganización emergente surge de las propiedades celulares intrínsecas en un entorno uniforme.
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