Functional and Transcriptomic Characterization of iPSC-derived Macrophages and their Application in Modeling Mendelian Disease

Using RNA-Seq, we reported novel findings in the comparison of transcriptome profiles of isogenic HMDM and IPSDM during differentiation and polarization. First, IPSDM lost expression of pluripotency markers, had remarkably distinct gene expression profiles relative to precursor iPSCs, and had largely similar gene expression as HMDM. Second, macrophage polarization to M1 was associated with a dramatic change in the transcriptome; expression profiles of IPSDM- and HMDM-derived M1 lines were highly correlated with each other but much less so with their respective IPSDM and HMDM precursors. Third, M2-HMDM lines had limited difference in gene expression compared to their non-polarized precursors, likely due to the known M2-like phenotype of M-CSF differentiated macrophages and their similarity to the IL-4 derived M2 phenotype Finally, through RNA-Seq we identified many new genes modulated during polarization in both HMDM and IPSDM thus providing novel, and potentially regulatory, candidates that warrant further study. Overall design: iPS, IPSDM (including M1/M2) and HMDM (including M1/M2)cells were sequenced by Illumina HiSeq 2000 with poly-A selection

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Zhang H, Xue C, Shah R, Bermingham K, Hinkle CC, Li W, Rodrigues A, Tabita-Martinez J, Millar JS, Cuchel M, Pashos EE, Liu Y, Yan R, Yang W, Gosai SJ, VanDorn D, Chou ST, Gregory BD, Morrisey EE, Li M, Rader DJ, Reilly MP