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Accesibilidad diferencial de la cromatina, expresión génica y empalme de ARNm entre las células ciliadas cocleares
Chuan Zhi Foo1,2, Anne Duggan1, Elizabeth T Bartom3
1Department of Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
Journal of the Association for Research in Otolaryngology : JARO
|September 5, 2025
Resumen
Las células ciliadas internas y externas en desarrollo en la cóclea muestran una expresión génica y patrones de empalme distintos, regulados por la accesibilidad de la cromatina. Esta investigación ofrece información sobre las bases moleculares de la audición y la sordera.
Área de la Ciencia:
- La genómica
- La epigenética
- Biología del desarrollo
Sus antecedentes:
- Las células ciliadas cocleares de mamíferos, internas (IHC) y externas (OHC), son cruciales para la audición.
- La disfunción o pérdida de estas células conduce a la sordera congénita y adquirida.
- Los IHC y los OHC poseen transcriptomas distintos durante el desarrollo.
Objetivo del estudio:
- Investigar la regulación del nivel de cromatina de la expresión génica diferencial en el desarrollo de IHC y OHC.
- Explorar las diferencias en el empalme de ARNm entre los HCI en desarrollo y los HCO.
- Determinar si las diferencias de accesibilidad de la cromatina explican la expresión génica diferencial.
Principales métodos:
- Secuenciación masiva de ARN de los IHC y OHC en desarrollo de ratones para analizar los transcriptomas.
- Secuenciación ATAC a granel de los IHC y OHC en desarrollo de ratones para mapear la accesibilidad a la cromatina.
- Análisis comparativo de los datos de ARN-seq y ATAC-seq para vincular la expresión génica con los estados de la cromatina.
Principales resultados:
- Se observó una accesibilidad diferencial de la cromatina en los promotores de muchos genes expresados diferencialmente en el desarrollo de IHC y OHC.
- Tanto los genes transitorios de desarrollo como los genes con expresión adulta sostenida mostraron una accesibilidad distinta a la cromatina.
- El empalme de ARNm alternativo y los sitios de inicio de transcripción contribuyen a la diversidad transcriptómica.
- Las células ciliadas cocleares exhiben promotores únicos y isoformas de ARNm que no se encuentran en otros tipos de células.
Conclusiones:
- La expresión génica diferencial en los tipos de células ciliadas en desarrollo está controlada por mecanismos pre- y post-transcripcionales.
- Los promotores únicos y las isoformas de ARNm en las células ciliadas cocleares subrayan la importancia de estudiar los transcriptomas y epigenomas de tipos celulares raros.
- Se proporciona un recurso de acceso público para visualizar promotores de genes y isoformas de ARNm en células ciliadas neonatales.
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