Wilms Tumor 1b Expression Defines a Pro-regenerative Macrophage Subtype and Is Required for Organ Regeneration in the Zebrafish

Wilms 肿瘤 1b 表达定义促再生巨噬细胞亚型,并且是斑马鱼器官再生所必需的

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作者:Andrés Sanz-Morejón, Ana B García-Redondo, Hanna Reuter, Inês J Marques, Thomas Bates, María Galardi-Castilla, Andreas Große, Steffi Manig, Xavier Langa, Alexander Ernst, Indre Piragyte, Marius-Alexandru Botos, Juan Manuel González-Rosa, Marta Ruiz-Ortega, Ana M Briones, Mercedes Salaices, Christoph

Abstract

Organ regeneration is preceded by the recruitment of innate immune cells, which play an active role during repair and regrowth. Here, we studied macrophage subtypes during organ regeneration in the zebrafish, an animal model with a high regenerative capacity. We identified a macrophage subpopulation expressing Wilms tumor 1b (wt1b), which accumulates within regenerating tissues. This wt1b+ macrophage population exhibited an overall pro-regenerative gene expression profile and different migratory behavior compared to the remainder of the macrophages. Functional studies showed that wt1b regulates macrophage migration and retention at the injury area. Furthermore, wt1b-null mutant zebrafish presented signs of impaired macrophage differentiation, delayed fin growth upon caudal fin amputation, and reduced cardiomyocyte proliferation following cardiac injury that correlated with altered macrophage recruitment to the regenerating areas. We describe a pro-regenerative macrophage subtype in the zebrafish and a role for wt1b in organ regeneration.

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