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La comunicación celular heterotípica regula la multipotencia de las células madre glandulares

Alessia Centonze1, Shuheng Lin1, Elisavet Tika1

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Las células luminales (LC) normalmente suprimen la multipotencia de las células madre basales (BSC) en las glándulas. La eliminación de las LC permite que las BSC recuperen la multipotencia de tipo embrionario, revelando una vía de comunicación clave para mantener la identidad de las células madre.

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Área de la Ciencia:

  • Biología de las células madre
  • Biología epitelial
  • Señales celulares

Sus antecedentes:

  • El epitelio glandular, como el mamario y la próstata, está formado por células basales (BC) y células luminales (LC).
  • Las células madre basales adultas (CSB) suelen ser unipotentes, pero pueden recuperar la multipotencia durante la regeneración o la activación de oncogenes.
  • Actualmente se desconoce el mecanismo que restringe la multipotencia de BSC en condiciones fisiológicas normales.

Objetivo del estudio:

  • Investigar el mecanismo que restringe la multipotencia de las células madre basales en el epitelio glandular.
  • Identificar los actores celulares y moleculares involucrados en el mantenimiento de la fidelidad del linaje.

Principales métodos:

  • Se ha investigado la multipotencia de BSC in vivo (en ratones) e in vitro (en organoides) después de la ablación de células luminales (LC).
  • Se utilizó la secuenciación de ARN a granel y de una sola célula para analizar los cambios en la expresión génica en los BSC.
  • Interacciones ligando-receptor previstas a partir de datos de una sola célula para identificar las vías de señalización.

Principales resultados:

  • La ablación LC reactivó la multipotencia BSC, induciendo un programa híbrido de diferenciación de células basales y luminales.
  • El factor de necrosis tumoral (TNF), secretado por las LC, fue identificado como un inhibidor clave de la multipotencia BSC.
  • Las vías de Notch, Wnt y EGFR se activaron tras la ablación de la LC; su inhibición o estimulación del TNF bloquearon la multipotencia del BSC.

Conclusiones:

  • La comunicación heterotípica entre las LC y las BC es crucial para mantener la fidelidad del linaje en las células madre epiteliales glandulares.
  • La señalización de TNF de las LC suprime activamente la multipotencia BSC en condiciones fisiológicas normales.
  • La comprensión de esta comunicación proporciona información sobre la regulación de las células madre y los posibles objetivos terapéuticos.