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Gene expression profiling of skin melanophages and macrophages positive or negative for MHC class II expression

ABSTRACT: The lack of mouse models permitting the specific ablation of tissue-resident macrophages and monocyte-derived cells complicates understanding of their contribution to tissue integrity and to immune responses. Here we use a new model permitting diphtheria-toxin (DT)-mediated depletion of those cells and in which dendritic cells are spared. We showed that the myeloid cells of the mouse ear skin dermis are dominated by a population of melanin-laden macrophages, called melanophages, that has been missed in most previous studies. By using gene expression profiling, DT-mediated ablation and parabiosis, we determined their identity including their similarity to other skin macrophages, their origin and their dynamics. Limited information exist on the identity of the skin cells responsible for long-term tattoo persistence. Benefiting of our knowledge on melanophages, we showed that they are responsible for retaining tattoo pigment particles through a dynamic process which characterization has direct implications for improving strategies aiming at removing tattoos.

ORGANISM(S): Mus musculus

PROVIDER: GSE103339 | GEO | 2018/02/21

REPOSITORIES: GEO

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Project description:Products of adipocytes control bone cells and may therefore lead to new anti-osteoporosis therapies. To address this issue we mated mice expressing the primate diphtheria toxin receptor (DTR), which is equivalent to Heparin Binding Epidermal Like Growth Factor (HB-EGF), under control of a Stop-flox cassette, to those expressing adiponectin-Cre (ADQ-Cre). Injected diphtheria toxin (DT) completely eliminates white and brown adipose tissue in these DTRADQ mice and ablates marrow adipocytes. Medullary bone of DTRADQ mice begins to accumulate, due to stimulated osteoblast recruitment and differentiation, within 4 days of injected DT. By 10-14 days of DT administration to DTRADQ mice, trabecular bone has increased 1000%. Two months after fat ablation, cortical thickness has markedly increased as has bone strength. To gain insight into the signaling events by which DT/DTRADQ adipocyte ablation promotes osteogenesis we performed RNAseq analysis of marrow prior to and after 1-3 days of DT injection. This exercise confirms ablation of marrow adipocytes, as adiponectin expression is markedly reduced while enhanced expression of Col1a1 and Col1a2 genes is in keeping with stimulated osteogenesis. RNAseq analysis also indicates that DT/DTRADQ-induced osteogenesis is mediated by the BMPR pathway. For example, there is suppressed genetic expression of the specific BMPR inhibitors, chordin-like1 (CHRDL1) and gremlin1 (GREM1). This adipocyte ablation-mediated increase in bone mass is due to cooperative activation of BMP and EGF receptor signaling as adipocyte-produced inhibitors are suppressed and downstream targets activated or expressed. Medicinal inhibition of either signaling pathway prevents induction of the osteosclerotic phenotype. DTR-induced post-natal osteogenesis does not represent the products of peripheral fat depots and is more likely due to those of marrow adipocytes. Thus, anabolic drugs activating both BMP and EGF receptor signaling may be a means of profoundly increasing bone mass and treating osteoporosis.

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Gene expression profiling of skin melanophages and macrophages positive or negative for MHC class II expression

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