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Chunk #20 — Results — SPI1 (PU.1) cistrome and functional analysis in myeloid cells

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A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer's disease.
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To further explore the functional impact of variation in SPI1 expression, we performed qPCR to test whether differential Spi1 expression in BV2 cells can modulate expression of genes thought to play important roles in AD pathogenesis and/or microglial cell function (Fig. 3, Supplementary Fig. 9, Supplementary Table 13, 14). We found that levels of some of these genes were affected in opposing directions by overexpression and knock-down of Spi1 (Fig. 4a), while other genes were affected only by overexpression (Fig. 4b) or knock-down (Fig. 4c) or not affected at all (Supplementary Fig. 9). After knock-down of Spi1 in BV2 cells, expression of Cd33, Tyrobp, Ms4a4a and Ms4a6d decreased and expression of Apoe and Clu/ApoJ increased (Fig. 4a, 4c). These data demonstrate that multiple microglial genes, some already implicated in AD, are selectively perturbed by altered expression of Spi1.