Bulk RNA-seq of iPSC-derived macrophages exposed to disease-relevant stimuli

Monocyte-derived macrophages (MDMs) are widely used to study human macrophage biology in vitro. However, use of MDMs as an experimental system is limited by donor-to-donor variability, the total cell availability and pre-activation effects . Here we generated iPSC- derived macrophages (iDMs) with high yield and low phenotypic and functional variability. We used iDMs to model disease-relevant phenotypes and mapped their transcriptomes to inflammatory conditions (IBD). Using this approach, we found that the transcriptomic phenotypes generated in vitro closely correlate to macrophage phenotypes present in disease. Overall design: iPSC-derived macrophages (IDMs) from 6 batches were stimulated with TNFa, IFNg, IL1b, and TGFb to compare the downstream signaling induced by these different cytokines and assess the relevance of this in-vitro model for drug discovery purposes.