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Dinámica del desarrollo y la evolución de los elementos cis-reguladores en las células cerebelares del ratón
Ioannis Sarropoulos1, Mari Sepp1, Robert Frömel2
1Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, D-69120 Heidelberg, Germany. h.kaessmann@zmbh.uni-heidelberg.de s.pfister@dkfz.de i.sarropoulos@zmbh.uni-heidelberg.de m.sepp@zmbh.uni-heidelberg.de.
Science (New York, N.Y.)
|August 27, 2021
Resumen
Este estudio mapea el desarrollo del cerebelo de ratón utilizando el ensayo de un solo núcleo para la cromatina accesible a la transposasa utilizando la secuenciación (snATAC-seq). Revela la regulación dinámica de los genes y los patrones de conservación evolutiva en las células cerebelares.
Área de la Ciencia:
- La genómica
- Biología del desarrollo
- La neurociencia
Sus antecedentes:
- El desarrollo de órganos se basa en intrincadas redes reguladoras de genes.
- Comprender el desarrollo del cerebelo es crucial para la neurociencia.
- Los estudios anteriores no han aclarado completamente la dinámica reguladora durante el desarrollo cerebeloso.
Objetivo del estudio:
- Investigar la base reguladora del desarrollo del cerebelo del ratón en múltiples etapas.
- Identificar los tipos de células y los elementos cis-reguladores candidatos (ECR) en el cerebelo en desarrollo.
- Para explorar la conservación evolutiva de los elementos reguladores en las células cerebelares.
Principales métodos:
- Ensayos adquiridos de un solo núcleo para la cromatina accesible a la transposasa utilizando perfiles de secuenciación (snATAC-seq) para aproximadamente 90.000 células en 11 etapas de desarrollo.
- Tipos de células cerebelares mapeados y CREs candidatos identificados.
- Se compararon los datos genómicos con los genomas de los vertebrados y los datos del snATAC-seq cerebeloso de la zarigüeya.
Principales resultados:
- Se detectó una heterogeneidad espacial temporal significativa en las células progenitoras.
- Se observó una divergencia gradual en los programas reguladores de la diferenciación de las neuronas cerebelares.
- Se encontró una disminución compartida en la conservación de CRE durante el desarrollo y la diferenciación entre el ratón y la zarigüeya, con diferencias específicas de tipo celular en la restricción.
Conclusiones:
- Delineó la dinámica del desarrollo y la evolución de la regulación génica en las células cerebelares.
- Proporcionó información sobre el desarrollo de órganos de mamíferos y los mecanismos reguladores del cerebelo.
- Se destacan las estrategias reguladoras conservadas y divergentes en la evolución cerebelosa.
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