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La interacción entre las identidades metabólicas en la cripta intestinal apoya la función de las células madre

Maria J Rodríguez-Colman1, Matthias Schewe2, Maaike Meerlo1

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Resumen

El metabolismo alimenta la renovación de las células madre intestinales. Las células de Paneth proporcionan lactato a las células madre Lgr5+, apoyando la función mitocondrial y la diferenciación a través de la señalización de especies reactivas de oxígeno.

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Área de la Ciencia:

  • Gastroenterología
  • Biología celular
  • El metabolismo

Sus antecedentes:

  • El epitelio del intestino delgado se renueva rápidamente, impulsado por células madre Lgr5+ ubicadas en la base de la cripta.
  • Si bien se conocen las vías de señalización que regulan la función de las células madre, las contribuciones metabólicas a la homeostasis epitelial siguen siendo en gran medida inexploradas.

Objetivo del estudio:

  • Para investigar los distintos programas metabólicos de las células madre intestinales y las células de Paneth.
  • Para aclarar el papel del metabolismo celular en el mantenimiento de la homeostasis epitelial intestinal y la función de las células madre.

Principales métodos:

  • Aislamiento de glóbulos blancos Lgr5+ y células Paneth del intestino delgado de ratón.
  • Evaluación de la actividad mitocondrial y la glucólisis.
  • Inhibición de la actividad mitocondrial y la glucólisis.
  • Pruebas de formación de organoides.
  • Análisis de la señalización por especies reactivas de oxígeno y la activación de la MAPK p38.

Principales resultados:

  • Los Lgr5+ CBC muestran una mayor actividad mitocondrial en comparación con las células de Paneth.
  • La inhibición de la actividad mitocondrial en los glóbulos rojos Lgr5+ perjudica la función de las células madre.
  • La inhibición de la glucólisis en las células de Paneth también afecta la función de las células madre.
  • Las células Paneth suministran lactato a los Lgr5+ CBC, apoyando su fosforilación oxidativa.
  • La fosforilación oxidativa activa la p38 MAPK a través de la señalización ROS, promoviendo la maduración de la cripta.

Conclusiones:

  • Los distintos programas metabólicos en las células Lgr5+ y las células Paneth son cruciales para la función de las células madre intestinales.
  • El lactato derivado de las células de Paneth apoya el metabolismo y la diferenciación de Lgr5+ CBC.
  • La fosforilación oxidativa mitocondrial y la señalización ROS son impulsores clave de la diferenciación celular en la cripta intestinal.