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Registro simbólico de la actividad de los elementos de señalización y cisregulación en el ADN
Wei Chen1,2, Junhong Choi3,4,5,6, Xiaoyi Li3,6
1Department of Genome Sciences, University of Washington, Seattle, WA, USA. wchen108@uw.edu.
Nature
|July 17, 2024
Resumen
Este estudio introduce el registro genómico impulsado por el potenciador de la actividad transcripcional en multiplex (ENGRAM), un nuevo método para registrar de manera estable las actividades celulares en el genoma. ENGRAM permite un registro de alta fidelidad y multiplexación de la expresión génica y las vías de señalización a lo largo del tiempo.
Área de la Ciencia:
- Biología molecular
- La genómica
- Biología de sistemas
Sus antecedentes:
- Los métodos convencionales para medir la expresión génica y la transducción de señales requieren la destrucción de muestras o imágenes en vivo.
- Se necesita un registro estable y a largo plazo de las actividades biológicas dentro de las células.
Objetivo del estudio:
- Desarrollar un nuevo paradigma para registrar de manera estable las actividades biológicas en el genoma.
- Demostrar la capacidad del registro genómico impulsado por el potenciador de la actividad transcripcional en multiplex (ENGRAM) para el registro multiplexado de alta fidelidad.
Principales métodos:
- ENGRAM utiliza la producción dependiente de la señal de ARN guía de edición principal para insertar códigos de barras específicos de la señal en una unidad de registro genómico.
- La estrategia se aplicó al registro múltiple de elementos cis-reguladores y vías de transducción de señales (WNT, NF-κB, Tet-On).
- ENGRAM se combinó con la edición secuencial del genoma (máquina de escribir ADN) para el registro temporal de las vías de señalización ortogonales y se aplicó a la diferenciación de células madre embrionarias de ratón.
Principales resultados:
- Registro múltiple demostrado de alta fidelidad, sensible y reproducible de actividades específicas del tipo de célula.
- Se logró un registro genómico dependiente del tiempo y la concentración de las actividades de WNT, NF-κB y Tet-On.
- Se ha registrado con éxito la actividad del factor de transcripción transitorio a través de la diferenciación de células madre embrionarias de ratón en gastruloides.
Conclusiones:
- ENGRAM proporciona un nuevo método para el registro genómico estable de señales y estados biológicos.
- Esta tecnología tiene un amplio potencial para complementar los paradigmas de medición existentes en los sistemas biológicos.
- Se necesita un mayor desarrollo para realizar plenamente el potencial del registro genómico.
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