Optimised generation of iPSC-derived macrophages and dendritic cells that are functionally and transcriptionally similar to their primary counterparts

Abstract

Induced pluripotent stem cells (iPSC) offer the possibility to generate diverse diseaserelevant cell types, from any genetic background with the use of cellular reprogramming and directed differentiation. This provides a powerful platform for disease modeling, drug screening and cell therapeutics. The critical question is how the differentiated iPSCderived cells translate to their primary counterparts. Our refinement of a published differentiation protocol produces a CD14+ monocytic lineage at a higher yield, in a smaller format and at a lower cost. These iPSC-derived monocytes can be further differentiated into macrophages or dendritic cells (DC), both with similar morphological and functional profiles as compared to their primary counterparts. Transcriptomic analysis of iPSCderived cells at different stages of differentiation as well as comparison to their bloodderived counterparts demonstrates a complete switch of iPSCs to cells expressing a monocyte, macrophage or DC specific gene profile. iPSC-derived macrophages respond to LPS treatment by inducing expression of classic macrophage pro-inflammatory response markers. Interestingly, though iPSC-derived DC show similarities to monocyte derived DC, they are more similar transcriptionally to a newly described subpopulation of AXL+ DC. Thus, our study provides a detailed and accurate profile of iPSC-derived monocytic lineage cells. Copyright: