Comparative genomic analysis of basal and LPS-induced expression patterns of bone marrow derived macrophages and bone marrow resident macrophages. Mus musculus

Comparative genomic analysis of basal and LPS-induced expression patterns of bone marrow derived macrophages and bone marrow resident macrophages demonstrates completely divergent transcriptome profile and indicates/confirms the existance of two distinct monocyte/macrophage populations in murine bone marrow. Most resident tissue macrophages descent from embryonic precursors of the yolk sac but inflammatory and bone marrow (BM) macrophages are considered to develop from hematopoietic stem cells (HSCs) in the BM. We now identified a novel subpopulation of resident CD163+ macrophages in the BM which were phenotypically and functionally distinct from classical BM-derived macrophages. Bioinformatics analysis of transcriptoms indicated a unique immune-modulatory phenotype of CD163+ macrophages. Cell fate studies in Csf1rMer-iCre-Mer;RosaLSL-GFP mice demonstrated that resident CD163+ macrophages of the BM do not develop from HSCs but descent from embryonic progenitors in the yolk sac strictly dependent on transcription factor IRF8. In contrast to other yolk sac derived tissue macrophages CD163+ cells seem to play a relevant role in infections and sterile inflammation. IRF8-/- mice lacking this population are highly sensible to S. aureus infections. Thus, CD163 defines a macrophage population resident in the bone marrow but originating from yolk sac progenitors which exhibits immune-modulatory properties under different inflammatory conditions. We used quantitative RNA-seq to perform whole transcriptome analysis and compare the transcriptomes of resident CD163+ BM macrophages and classical CD163- BMDM in steady state and after LPS stimulation. Overall design: Murine resident CD163+ macrophages from BM and classical CD163- BMDM were stimulated with LPS or left untreated and subsequently selected for RNA extraction and transcriptome comperative analysis using Illumina mRNA-sequencing (RNA-seq).