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Mutations in MAFB that cause Multicentric Carpo Tarsal Osteolysis (MCTO) affect the transcriptome of M-MØ

ABSTRACT: Macrophage phenotypic and functional heterogeneity derives from tissue-specific transcriptional signatures shaped by the local microenvironment. Most studies addressing the molecular basis for macrophage heterogeneity have focused on murine cells, while the factors controlling the functional specialization of human macrophages are less known. M-CSF drives the generation of human monocyte-derived macrophages with a potent anti-inflammatory activity upon stimulation. The contribution of MAFB to the homeostatic/anti-inflammatory macrophage profile is further supported by the skewed polarization of monocyte-derived macrophages from Multicentric Carpo Tarsal Osteolysis (OMIM#166300), a pathology caused by mutations in the MAFB gene.

ORGANISM(S): Homo sapiens

PROVIDER: GSE155883 | GEO | 2023/07/14

REPOSITORIES: GEO

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Mutations in MAFB that cause Multicentric Carpo Tarsal Osteolysis (MCTO) affect the transcriptome of M-MØ

Project description:Macrophage phenotypic and functional heterogeneity derives from tissue-specific transcriptional signatures shaped by the local microenvironment. Most studies addressing the molecular basis for macrophage heterogeneity have focused on murine cells, while the factors controlling the functional specialization of human macrophages are less known. M-CSF drives the generation of human monocyte-derived macrophages with a potent anti-inflammatory activity upon stimulation. We now report that knock-down of MAFB impairs the acquisition of the anti-inflammatory profile of human macrophages, identify the MAFB-dependent gene signature in human macrophages and illustrate the co-expression of MAFB and MAFB-target genes in CD163+ tissue-resident and tumor associated macrophages. The contribution of MAFB to the homeostatic/anti-inflammatory macrophage profile is further supported by the skewed polarization of monocyte-derived macrophages from Multicentric Carpo Tarsal Osteolysis (OMIM#166300), a pathology caused by mutations in the MAFB gene. Our results demonstrate that MAFB critically determines the acquisition of the anti-inflammatory transcriptional and functional profiles of human macrophages.

2019-05-03 | GSE84616 | GEO

MAFB controls the acquisition of the anti-inflammatory transcriptional profile of M-MØ.

2019-05-03 | GSE84617 | GEO

Multicentric Carpo-Tarsal Osteolysis Syndrome Mimicking Juvenile Idiopathic Arthritis: Two Case Reports and Review of the Literature.

Project description: Not available

| S-EPMC8554157 | biostudies-literature

Initiation of organ maturation and fruit ripening in grapevine is controlled by the CARPO-NAC transcription factor [Syrah]

Project description:In this study we identified the NAC family member VviCARPO (Controlled Adjustment of Ripening and maturation of Plant Organs) as a key regulator of grapevine maturation. We explored CARPO binding landscapes through DAP-seq and overlapped its bound genes with transcriptomics datasets from stable and transient CARPO overexpressing grapevine plants to narrow a set of high-confidence targets. Among these, we identified key molecular ripening markers. Physiological, metabolic and promoter activation analyses showed that CARPO induces chlorophyll degradation and anthocyanin accumulation through the up regulation of VviSGR1 and VviMYBA1, respectively, with the latter being up-regulated by a VviCARPO-VviNAC03 regulatory complex. CARPO complemented the nor mutant phenotype in tomato, suggesting it may have acquired a dual role as an orchestrator of both ripening- and senescence-related processes. Our results evidenced that CARPO is a master regulator of the grapevine vegetative-to-mature phase organ transition and therefore an essential target for insuring fruit quality and environmental resilience.

2021-10-07 | GSE185448 | GEO

Initiation of organ maturation and fruit ripening in grapevine is controlled by the CARPO-NAC transcription factor [Sultana]

2021-10-07 | GSE185447 | GEO

Homo sapiens

Project description:Mutations in MAFB that cause Multicentric Carpo Tarsal Osteolysis (MCTO) affect the transcriptome of M-MØ

| PRJNA330670 | ENA

Non adherent macrophage of mafb null and WT

Project description:MafB is a member of the large Maf family of transcription factors that share similar basic region/leucine zipper DNA binding motifs and N-terminal activation domains.Although it is well known that MafB is specifically expressed in macrophages, characterization of the null mutant phenotype in these tissues has not been previously reported. To investigate suspected MafB functions macrophages, we generated mafB/green fluorescent protein (GFP) knock-in null mutant mice. MafB deficiency was found to dramatically suppress F4/80 expression in nonadherent macrophages. To investigate detail function of MafB in nonadherent macrophages, we performed microarray analysis. Macrophages were derived from day 14.5 fetal livers of mafB- /- and WT mice. Suspensions of single fetal liver cells were prepared by mechanical disruption . A total of 106 cells in suspension were centrifuged at 1,200 rpm for 5 min, and the cell pellet was resuspended in Dulbeccoâs modified Eagleâs medium supplemented with 10% fetal calf serum (heat inactivated), streptomycin and penicillin (100 units/ml), and macrophage colony-stimulating factor (M-CSF) (10 ng/ml) and then seeded either onto a nonadhesive dishes coated with hydrophilic polymers (Hydrocell; Cell Seed, Tokyo). The culture medium was not changed throughout the experiment. M-CSF (final concentration, 10 ng/ml) was added every day from day 4 onwards. One, 2, 4, and 6 days after seeding, the cells were harvested and analyzed by flow cytometry. After 6 day culture, macrophages of Mafb-/- and WT were use microarray analysis .

2010-02-27 | E-GEOD-20419 | biostudies-arrayexpress

Physical exercise on proteoglycan_induced arthritis (PGIA) mice_transcriptome responses on tarsal joint

Project description:Gene expression profiles in the tarsal bones and joints of mice that performed treadmill exercise vs. those who were not exercised were compared. Exercise induced the downregulation of genes and signaling pathways that mediates and promotes the inflammatory process and triggered the upregulation of genes associated to cartilage remodeling and bone mineralization.

2017-09-12 | GSE103686 | GEO

Levofloxacin induces the downexpression of inflammation-related transcriptome in the tarsal joint of Spondyloarthritis DBA/1 mice.

Project description:Gene expression profiles in the tarsal joints of DBA/1 mice whit spontaneus arthritis and treated with levofloxacion vs. those who were not received levofloxacin were compared. Levofloxacin induced the downexpression of inflammation-related genes and signaling pathways.

2022-10-22 | GSE216172 | GEO

Transcriptional effects of siRNA-mediated MAFB knockdown on SARS-CoV-2-infected human M-CSF and GM-derived macrophages.

Project description:To investigate the MAFB-dependent genes in the SARS-COV-2 infection on human macrophages, we generated M-CSF and GM-CSF-dependent monocyte-derived macrophages in which MAFB has been knocked down by siRNA and then infected with SARS-CoV-2. Monocytes from three independent donors (0.5 x 106 cells/ml, >95% CD14+ cells) were cultured in RPMI 1640 supplemented with 10% fetal bovine serum (FBS) at 37°C in a humidified atmosphere with 5% CO2 for 6 days in the presence of GM-CSF or M-CSF, with cytokine addition every two days. Then, monocyte-derived macrophages were transfected with MAFB-specific siRNA or control siRNA, kept in culture for 6 hours, and then were exposed to SARS-CoV-2 (SARS-CoV-2 clinical isolate Gisaid EPI_ISL_1120962, corresponding to ancestral S D614G, at an MOI=1) or uninfected. After 36 hours, cells were lysed and RNA isolated for transcriptional analysis. We performed gene expression profiling analysis using data obtained from RNA-seq of 3 different donors.

2024-02-08 | GSE224131 | GEO

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