RNAseq of untreated, CSF1-treated, CSF1+QVD-treated, and GM-CSF-treated monocytes

Caspases, which are key effectors of apoptosis, have demonstrated non-apoptotic functions. One of these functions is the differentiation into macrophages of peripheral blood monocytes exposed to Colony-Stimulating Factor-1 (CSF1). Conversely, GM-CSF induces the differentiation of monocytes into macrophages in a caspase-independent manner. Macrophages generated by CSF1 and GM-CSF have distinct polarity. Macrophage polarization plays an important role in the pathogenesis of diverse human diseases as cancer, leading us to explore if caspase inhibition would affect macrophage polarization. To explore the role of caspases in CSF1 differentiation, we used human monocytes sorted from buffy coats treated by cytokines. We reported that caspase inhibition delays the ex vivo differentiation of peripheral blood monocytes exposed to CSF1 and modifies the phenotype of generated macrophages, e.g. cell shape, surface markers. Moreover, by RNAseq, we observed that the macrophages generated in presence of CSF1 and QVD are different from CSF1-treated monocytes and from GM-CSF-treated monocytes. Cell cycle and focal adhesion-related pathway genes were selectively down-regulated. This study confirms the importance of caspase activation in CSF1 differentiation.