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La conmutación del destino axial de las nefronas demuestra un sistema plástico sintonizable bajo demanda
MaryAnne A Achieng1, Jack Schnell1, Connor C Fausto1
1Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at University of Southern California, Los Angeles, CA, USA.
Nature communications
|August 25, 2025
Resumen
El desarrollo del nefrón humano se basa en vías de señalización integradas de WNT, BMP y FGF. La comprensión de estos mecanismos en los organoides renales revela plasticidad y potencial para generar células nefrónicas.
Área de la Ciencia:
- Nefrología
- Biología del desarrollo
- Biología de las células madre
Sus antecedentes:
- El nefrón humano, crucial para la homeostasis, se desarrolla ~ 1 millón de unidades por riñón durante la gestación.
- Los mecanismos precisos que rigen el patrón axial de la nefrona humana siguen siendo poco conocidos.
Objetivo del estudio:
- Investigar los mecanismos de patrón axial en el desarrollo del nefrón humano.
- Utilización de organoides renales derivados de células madre pluripotentes inducidas (iPSC) para el estudio de la nefrogénesis.
- Comparar el desarrollo de los organoides con el desarrollo del riñón humano in vivo.
Principales métodos:
- El uso de organoides renales derivados de iPSC para generar nefronas sincronizadas.
- Utilizando análisis transcriptómicos unicelulares y espaciales.
- Manipulando las vías de señalización WNT, BMP y FGF.
Principales resultados:
- El patrón de los nefrones humanos está orquestado por la señalización integrada WNT / BMP / FGF.
- Un estado activado por WNT / BMP suprimido promueve la identidad del nefrón distal, madurando en un grueso bucle ascendente de células de Henle a través de FGF.
- La supresión del FGF induce un estado celular proximal, dependiente de la señalización de BMP, destacando la plasticidad del desarrollo.
Conclusiones:
- La señalización integrada de WNT, BMP y FGF controla el patrón axial del nefrón humano.
- Los sistemas organoides renales ofrecen información sobre la plasticidad del desarrollo de los nefrones.
- Esta investigación proporciona una base para la generación bajo demanda de células nefrónicas.
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