Macrophages play an essential role in the resolution of tissue damage through removal of necrotic cells, thus paving the way for tissue regeneration. Macrophages also directly support the formation ...of new tissue to replace the injury, through their acquisition of an anti-inflammatory, or M2, phenotype, characterized by a gene expression program that includes IL-10, the IL-13 receptor, and arginase 1. We report that deletion of two CREB-binding sites from the Cebpb promoter abrogates Cebpb induction upon macrophage activation. This blocks the downstream induction of M2-specific Msr1, Il10, II13ra, and Arg-1 genes, whereas the inflammatory (M1) genes Il1, Il6, Tnfa, and Il12 are not affected. Mice carrying the mutated Cebpb promoter (βΔCre) remove necrotic tissue from injured muscle, but exhibit severe defects in muscle fiber regeneration. Conditional deletion of the Cebpb gene in muscle cells does not affect regeneration, showing that the C/EBPβ cascade leading to muscle repair is muscle-extrinsic. While βΔCre macrophages efficiently infiltrate injured muscle they fail to upregulate Cebpb, leading to decreased Arg-1 expression. CREB-mediated induction of Cebpb expression is therefore required in infiltrating macrophages for upregulation of M2-specific genes and muscle regeneration, providing a direct genetic link between these two processes.
In this Scientists' Forum article, we present a new app, GENIGMA, launched by structural genomics specialist Marc A. Marti‐Renom and his team, aimed at mapping the 3D genome of cancer cell lines. ...GENIGMA is a digital game, which was designed and tested through a co‐creation process with citizens. Finally, by playing the game, citizens produce data, reaching beyond the capacity of artificial intelligence. This is an exceptional experiment of extreme citizen science, which broadens the implications of open science.
In this article of our Scientists' Forum, we present a new app, launched by structural genomics specialist Marc A. Marti‐Renom and his team, aimed at mapping the 3D genome of cancer cell lines. The app is a digital game, which was designed and tested through a co‐creation process with citizens. Finally, by playing the game, citizens produce data that goes beyond the capacity of artificial intelligence. This is an exceptional experiment of extreme citizen science, which broadens the implications of open science.
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