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Dinámica transcripcional y epigenética durante la especificación de células madre embrionarias humanas
Casey A Gifford1, Michael J Ziller, Hongcang Gu
1Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Cell
|May 14, 2013
Resumen
La diferenciación de células madre embrionarias humanas (hESC) revela cambios epigenéticos dinámicos durante la especificación de la capa germinal. La comprensión de estos eventos reguladores mejora las estrategias de diferenciación de células madre y los conocimientos sobre el desarrollo humano.
Área de la Ciencia:
- Biología del desarrollo Biología del desarrollo.
- Biología de las células madre Biología de las células madre
- La epigenética es la epigenética.
Sus antecedentes:
- Las células madre embrionarias humanas (hESC) ofrecen un modelo para estudiar las transiciones celulares humanas.
- La diferenciación dirigida de los hESC permite la investigación de los mecanismos reguladores del desarrollo temprano.
Objetivo del estudio:
- Profilar de manera exhaustiva los cambios transcripcionales y epigenéticos durante la diferenciación de la hESC en tres capas germinales embrionarias.
- Para identificar eventos reguladores clave y alteraciones epigenéticas asociadas con la especificación del linaje.
Principales métodos:
- Integración de secuenciación de bisulfito de genoma completo (WGBS), secuenciación de inmunoprecipitación de cromatina (ChIP-seq) y secuenciación de ARN (RNA-seq).
- Análisis de la metilación del ADN, las modificaciones H3K4me1 y H3K27me3 en poblaciones celulares diferenciadas.
- Examen de la actividad del elemento regulador y la unión del factor de transcripción.
Principales resultados:
- Se identificaron eventos transcripcionales y epigenéticos únicos para cada linaje de la capa germinal.
- Se observaron alteraciones dinámicas en la metilación del ADN y H3K4me1 en los elementos reguladores distales.
- El enriquecimiento H3K27me3 específico de la capa germinal se encontró en sitios con alta metilación del ADN en hESCs indiferenciadas.
Conclusiones:
- Estos hallazgos proporcionan información sobre el recableado epigenético de los programas reguladores humanos durante la diferenciación temprana.
- Una comprensión más profunda de estos eventos de especificación puede mejorar los protocolos de diferenciación dirigida para los hESC.
- Esta investigación contribuye a estrategias de diferenciación de células madre más fieles y a la comprensión del desarrollo humano.
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