Identifying suspect genes
A new study , led by Dr. Fadi Sheban, analyzed the functions of macrophages. “We began the research by analyzing macrophage datasets from human tumor samples and observing the various functions of these cells.”
“This analysis allowed us to identify 120 genes suspected of participating in the activation of the various pro-tumor functions of macrophages.”
Using advanced single-cell technologies, in conjunction with CRISPR-Cas9 gene editing, they removed individual macrophage genes in a single macrophage, and removed, one by one, the suspect genes to see how the properties of the macrophages were modified.
“Thanks to our newly developed platform, we were able to study the effects of the 120 suspected genes on the function of individual macrophages. This phase of the study included the sequencing of more than 100,000 edited macrophages in total ,” Sheban states.
Using a tool called MrVI, they simplified the data into a functional map showing how regulatory switches influence macrophage function. This is how the Zeb2 gene stood out on the map.
Because it completely altered the tumor-supporting activities of macrophages. Experiments performed in tissue cultures and in mice demonstrated that silencing the Zeb2 gene activates the antitumor mechanism of macrophages.
“We also conducted another analysis of human patient data and discovered that patients with high Zeb2 expression have a much higher risk of developing a more aggressive cancer.”
