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Controles del pH intracelular WNT aguas abajo de la glucólisis en embriones amnióticos
Masayuki Oginuma1,2,3, Yukiko Harima1,2, Oscar A Tarazona1,2
1Department of Genetics, Harvard Medical School, Boston, MA, USA.
Nature
|June 26, 2020
Resumen
Las células de brotes de cola embrionarias usan la glucólisis aeróbica, similar a las células cancerosas, para regular la señalización de WNT y promover el destino mesodérmico para el alargamiento del cuerpo. Este proceso metabólico influye en el destino celular durante el desarrollo.
Área de la Ciencia:
- Biología del desarrollo
- Metabolismo de las células
- Biología del cáncer
Sus antecedentes:
- La formación del cuerpo embrionario de los vertebrados se basa en la adición de tejido posterior desde el capullo de la cola.
- Las células de cogollos de cola presentan una alta glucólisis aeróbica (efecto Warburg), similar a las células cancerosas.
- La glucólisis regulada por el factor de crecimiento de los fibroblastos influye en la señalización de WNT en el brote de la cola.
Objetivo del estudio:
- Investigar el papel de la glucólisis en la regulación de la señalización de WNT dentro del capullo de la cola.
- Comprender cómo el estado metabólico influye en las decisiones del destino celular en el desarrollo de los embriones.
- Explorar el vínculo entre los programas metabólicos del desarrollo y el metabolismo de las células cancerosas.
Principales métodos:
- Se utilizaron embriones de pollo para estudios in vivo.
- Células humanas parecidas a brotes de cola diferenciadas in vitro de células madre pluripotentes inducidas.
- Gradientes de pH analizados, extrusión de lactato a través de simportores de monocarboxilato y acetilación de la β-catenina.
Principales resultados:
- Se observó un gradiente de pH invertido (pH extracelular más bajo que el pH intracelular) en las células de brotes de cola, similar a las células cancerosas.
- Se demostró que la glucólisis promueve la extrusión de lactato y protones, aumentando el pH intracelular.
- Se demostró que el pH intracelular elevado facilita la acetilación no enzimática de la β-catenina, promoviendo el destino mesodérmico.
Conclusiones:
- La glicólisis regula la señalización de WNT en las células de brotes de cola mediante la modulación del pH intracelular y la acetilación de la β-catenina.
- Esta vía metabólica es crucial para especificar el mesodermo paraxial y permitir el alargamiento axial.
- Los hallazgos sugieren que las células cancerosas pueden reactivar los programas metabólicos del desarrollo.
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