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El regulador negativo pan-ErbB Lrig1 es un marcador de células madre intestinales que funciona como supresor de
Anne E Powell1, Yang Wang, Yina Li
1Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Cell
|April 3, 2012
Resumen
Lrig1 marca las células madre intestinales en reposo que reponen el tejido dañado. La pérdida de Lrig1 interrumpe la señalización de ErbB, lo que lleva a adenomas intestinales, destacando su papel en la prevención de la neoplasia.
Área de la Ciencia:
- Biología celular Biología celular.
- Gastroenterología y Gastroenterología.
- Investigación del cáncer Investigación del cáncer.
Sus antecedentes:
- Las células madre intestinales (CIE) son cruciales para la homeostasis de los tejidos.
- Existen poblaciones de CSI tanto proliferativas (Lgr5+) como en reposo.
- Los mecanismos moleculares que regulan la quiescencia del ISC no se comprenden completamente.
Objetivo del estudio:
- Para identificar marcadores moleculares para las células madre intestinales en reposo.
- Para aclarar el papel de Lrig1 en la regulación de las células madre intestinales.
- Para investigar el vínculo entre la señalización Lrig1, ErbB y la neoplasia intestinal.
Principales métodos:
- El rastreo de linaje y el rastreo celular en modelos de ratón.
- Perfilado del transcriptoma de las células madre Lrig1+ y Lgr5+ del colon.
- Manipulación genética (pérdida de Apc, ablación de Lrig1) y análisis de la formación de tumores.
Principales resultados:
- Lrig1 identifica una población de ISCs quietos y de larga vida en la base de la cripta.
- Las CSI Lrig1+ exhiben perfiles de expresión génica distintos relacionados con la represión del ciclo celular y la respuesta al estrés oxidativo.
- La pérdida de Lrig1 conduce a un aumento de la señalización de ErbB y promueve la formación de adenoma duodeno.
- La pérdida de Apc en las células Lrig1+ induce adenomas intestinales.
Conclusiones:
- Lrig1 es un regulador clave de la quiescencia de las células madre intestinales.
- La señalización ErbB calibrada, influenciada por reguladores negativos como Lrig1, mantiene la quiescencia ISC.
- La alteración de la regulación mediada por Lrig1 predispone al desarrollo de cáncer intestinal.
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