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Multistabilidad sintética en células de mamíferos
Ronghui Zhu1, Jesus M Del Rio-Salgado1, Jordi Garcia-Ojalvo2
1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Science (New York, N.Y.)
|January 20, 2022
Resumen
Los investigadores diseñaron un circuito de genes sintéticos llamado MultiFate para una multistabilidad controlable en las células de mamíferos. Este circuito permite el control del estado celular a largo plazo y expandible, avanzando la biología sintética y la ingeniería del destino celular.
Área de la Ciencia:
- Biología sintética
- Redes de regulación genética
- Ingeniería de células de mamíferos
Sus antecedentes:
- Los organismos multicelulares utilizan circuitos reguladores de genes para la determinación del destino celular.
- La multistabilidad, la generación de estados celulares heredables, es crucial para el desarrollo.
- La ingeniería de circuitos multistables sintéticos es clave para comprender y controlar el destino celular.
Objetivo del estudio:
- Diseñar y crear un circuito genético sintético para una multistabilidad controlable y expandible en células de mamíferos.
- Investigar el potencial de los factores de transcripción diseñados para generar múltiples estados celulares estables.
- Para sentar las bases para la ingeniería de comportamientos multicelulares complejos.
Principales métodos:
- Desarrolló MultiFate, un circuito sintético inspirado en los mecanismos reguladores de genes naturales.
- Utilizó factores de transcripción de dedos de zinc diseñados que se autoactivan y se inhiben mutuamente.
- Diseño basado en modelos empleado para diseñar circuitos capaces de generar múltiples estados estables.
- Estabilidad y controlabilidad a largo plazo de los estados celulares modificados.
Principales resultados:
- Se han diseñado con éxito circuitos MultiFate capaces de generar hasta siete estados celulares mitoticamente heredables.
- Estabilidad demostrada a largo plazo de estos estados durante al menos 18 días.
- Mostró el cambio de estado controlado y la modulación de la estabilidad del estado a través de entradas externas.
- Confirmó la expansibilidad del circuito MultiFate con factores de transcripción adicionales.
Conclusiones:
- MultiFate proporciona una plataforma robusta para lograr multistabilidad a largo plazo, controlable y expandible en células de mamíferos.
- Este circuito sintético ofrece información sobre los mecanismos naturales de control del destino de las células.
- Los hallazgos establecen una base para la ingeniería de programas y comportamientos multicelulares sofisticados.
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