Forschern ist es gelungen, beschädigte Mäuseherzen mit einem Protein aus Zebrafischen zu reparieren. Sie entdeckten, dass das Protein Hmga1 eine Schlüsselrolle bei der Herzregeneration im Zebrafisch spielt. Bei Mäusen konnte dieses Protein das Herz wiederherstellen, indem es ruhende Reparaturgene aktivierte, ohne Nebenwirkungen zu verursachen.

**Cross-species comparison reveals that Hmga1 reduces H3K27me3 levels to promote cardiomyocyte proliferation and cardiac regeneration**

Abstract

In contrast to adult mammalian hearts, the adult zebrafish heart efficiently replaces cardiomyocytes lost after injury. Here we reveal shared and species-specific injury response pathways and a correlation between Hmga1, an architectural non-histone protein, and regenerative capacity, as Hmga1 is required and sufficient to induce cardiomyocyte proliferation and required for heart regeneration. In addition, Hmga1 was shown to reactivate developmentally silenced genes, likely through modulation of H3K27me3 levels, poising them for a pro-regenerative gene program. Furthermore, AAV-mediated Hmga1 expression in injured adult mouse hearts led to controlled cardiomyocyte proliferation in the border zone and enhanced heart function, without cardiomegaly and adverse remodeling. Histone modification mapping in mouse border zone cardiomyocytes revealed a similar modulation of H3K27me3 marks, consistent with findings in zebrafish. Our study demonstrates that Hmga1 mediates chromatin remodeling and drives a regenerative program, positioning it as a promising therapeutic target to enhance cardiac regeneration after injury.

[https://www.nature.com/articles/s44161-024-00588-9](https://www.nature.com/articles/s44161-024-00588-9)