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El ratón y el ser humano comparten programas de transcripción conservados para el desarrollo de las interneuronas
Yingchao Shi1, Mengdi Wang1,2, Da Mi3,4,5
1State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology (Shanghai), Institute of Biophysics, Chinese Academy of Sciences (CAS), BNU IDG/McGovern Institute for Brain Research, Beijing 100101, China.
Science (New York, N.Y.)
|December 9, 2021
Resumen
Las variaciones genéticas afectan a los trastornos del desarrollo neurológico al alterar células cerebrales específicas. Este estudio revela mecanismos conservados en el desarrollo del cerebro fetal humano para generar neuronas inhibidoras clave, cruciales para condiciones como el autismo y la esquizofrenia.
Área de la Ciencia:
- La neurociencia
- Biología del desarrollo
- La genética
Sus antecedentes:
- Los trastornos del desarrollo neurológico, incluidos el autismo y la esquizofrenia, están relacionados con alteraciones en poblaciones neuronales específicas.
- Las neuronas corticales y striatales que expresan ácido gamma-aminobutírico (GABAérgicas) están particularmente implicadas en estas condiciones.
- Comprender el desarrollo temprano de estas neuronas es fundamental para descifrar los mecanismos de la enfermedad.
Objetivo del estudio:
- Caracterizar la diversidad celular y las trayectorias de desarrollo de las neuronas GABAérgicas en el cerebro fetal humano.
- Investigar los programas de transcripción que gobiernan la especificación y diferenciación de estas neuronas.
- Comparar el desarrollo de neuronas GABAérgicas humanas con modelos de roedores establecidos.
Principales métodos:
- Se empleó secuenciación de ARN unicelular (scRNA-seq) para analizar las poblaciones celulares en las eminencias ganglionares humanas.
- Los datos de scRNA-seq se utilizaron para identificar la diversidad regional y temporal entre las células progenitoras.
- Se realizó un análisis computacional para inferir la lógica reguladora de la transcripción.
Principales resultados:
- Se identificó una diversidad regional y temporal significativa dentro de las células progenitoras de las eminencias ganglionares humanas.
- Caracterizó el surgimiento de diversas neuronas de proyección y interneuronas.
- Se encontró que los programas de transcripción para la especificación de neuronas GABAérgicas en humanos son similares a los de los roedores.
- Se revelaron mecanismos reguladores conservados que controlan el desarrollo de las neuronas GABAérgicas en el telencéfalo humano.
Conclusiones:
- Las eminencias ganglionares humanas exhiben una diversidad compleja de células progenitoras crucial para generar varios tipos de neuronas GABAérgicas.
- Las vías de desarrollo para las neuronas GABAérgicas humanas comparten una lógica reguladora conservada con los roedores.
- Estos hallazgos proporcionan información sobre la base evolutiva del desarrollo del cerebro humano y los trastornos del desarrollo neurológico.
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