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BLUEPRINT DNase accessibility of Epigenetic programming during monocyte to macrophage differentiation and trained innate immunity

Monocyte differentiation into macrophages represents a cornerstone process for host defense. Concomitantly, immunological imprinting of either tolerance or trained immunity determines the functional fate of macrophages and susceptibility to secondary infections. Transcriptomes and epigenomes in four primary cell types: monocytes, in vitro differentiated naïve, tolerized and trained macrophages were characterized. Inflammatory and metabolic pathways were modulated in macrophages, including decreased inflammasome activation, and pathways functionally implicated in trained immunity were identified. Strikingly, β-glucan training elicits an exclusive epigenetic signature, revealing a complex network of enhancers and promoters. Analysis of transcription factor motifs in DNase I hypersensitive sites at cell-type specific epigenetic loci unveiled differentiation and treatment specific repertoires. Altogether, this study provides a resource to understand the epigenetic changes that underlie innate immunity in humans.

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Dataset ID Description Technology Samples
EGAD00001001011 Illumina HiSeq 2000 NextSeq 500 57
EGAD00001001185 Illumina HiSeq 2000 2
EGAD00001001198 Illumina HiSeq 2000 14
EGAD00001001560 Illumina HiSeq 2000 2
EGAD00001001581 Illumina HiSeq 2000 16
EGAD00001002290 Illumina HiSeq 2000 4
EGAD00001002300 Illumina HiSeq 2000 2
EGAD00001002398 Illumina HiSeq 2000 4
EGAD00001002425 Illumina HiSeq 2000 4
EGAD00001002713 Illumina HiSeq 2000 25