Transcriptome analysis of LXR regulated genes in early differentiating and mature human macrophages

ABSTRACT: The objective of the study was to figure out the impact of LXR signaling on human macrophages. Primary human macrophages in an early differentiating and a mature differentiation state were treated with the LXR agonist T091317 for 4 and 24 h and transcriptome-wide expression analysis were performed. As LXRa is highly induced during macrophage differentiation and 68% of all LXRs targets change their expression during this process, we suggest that LXRs have essential functions in macrophage development. More than 238 genes are regulated in early as well as mature macrophages by activation of LXRs; most of them are up-regulated. LXRs administrate differentiation state specific as well as common macrophages functions related primarily to lipid homeostasis, immune response and cell fate. Interestingly, almost only genes related to lipid and cholesterol metabolism are overrepresented among early induced genes, whereas genes related to immune functions respond later, implying the existence of indirect mechanisms of control. Furthermore, in early differentiating macrophages cell proliferation and cell death associated genes are induced after 24 h of LXR activation, whereas in mature macrophages, showing high LXRa expression, the same functional cluster respond far earlier (4 h) after LXR ligand treatment. In conclusion, our data suggest that LXRs are modulators of macrophage differentiation, operating principally as positive transcriptional regulators of genes involved in lipid and cholesterol metabolism and by this indirectly influencing the immunophenotype of macrophages.

ORGANISM(S): Homo sapiens

PROVIDER: GSE35967 | GEO | 2014/12/19

SECONDARY ACCESSION(S): PRJNA151613

REPOSITORIES: GEO