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Los tumores cerebelares infantiles reflejan los programas de transcripción fetal conservados
Maria C Vladoiu1,2,3, Ibrahim El-Hamamy4,5, Laura K Donovan1,2
1Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
Nature
|May 3, 2019
Resumen
Los tumores cerebelares infantiles reflejan linajes celulares de desarrollo distintos. Este estudio revela que estos tumores cerebrales surgen de procesos de desarrollo temprano, lo que explica su incidencia máxima en niños pequeños.
Área de la Ciencia:
- La neurociencia
- Biología del desarrollo
- En el campo de la oncología
Sus antecedentes:
- El origen del tumor cerebeloso es complejo debido al desarrollo de la heterogeneidad de las células cerebelares.
- Comprender estos tumores requiere conocimientos sobre el desarrollo celular.
- Los estudios anteriores se enfrentaron a desafíos en la caracterización de diversos tipos de células cerebelares.
Objetivo del estudio:
- Investigar el origen celular y la base del desarrollo de los tumores cerebelares infantiles.
- Para identificar subgrupos moleculares de tumores cerebelares y sus linajes celulares correspondientes.
- Proporcionar una explicación del desarrollo para la alta incidencia de estos tumores en la primera infancia.
Principales métodos:
- Análisis de transcriptómica de una sola célula de más de 60.000 células cerebelares en desarrollo de ratón.
- Análisis comparativo de perfiles de transcripción de células tumorales con linajes celulares cerebelares en desarrollo.
- Transcriptómica de una sola célula de tumores cerebelares humanos en la infancia.
Principales resultados:
- Los diferentes subgrupos moleculares de tumores cerebelares infantiles reflejan linajes celulares cerebelares específicos y temporalmente restringidos.
- El medulloblastoma de Sonic Hedgehog se alinea con la jerarquía de las células granulares.
- El meduloblastoma del grupo 3 se asemeja a las células madre de Nestin+, el meduloblastoma del grupo 4 se asemeja a las células de cepillo unipolares, y el ependimoma / astrocitoma pilocítico se asemeja a las células progenitoras gliogénicas prenatales.
- Los tumores cerebelares humanos a menudo comprenden poblaciones de células mixtas con diferenciación divergente.
Conclusiones:
- Los tumores cerebelares infantiles representan un trastorno del desarrollo temprano del cerebro.
- Los orígenes celulares de estos tumores están vinculados a etapas específicas de desarrollo y tipos de células.
- Este vínculo de desarrollo ofrece una explicación aproximada de la incidencia máxima de tumores cerebelares en la primera infancia.
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