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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Myeloid lineage switch in pro-B cells generates novel macrophage subsets during homeostasis and inflammation

ABSTRACT: Here we demonstrate for the first time evidence of lineage switch from B-1 B lymphocyte to a macrophage , or so-called transdifferentiation, occurring in mature cells in vivo. Specifically, using transgenic B6.Mb1-iCre/Rosa26-YFP mice, in which YFP expression is restricted exclusively to B cell lineage, we discovered that a significant portion of tissue-resident macrophages in peritoneum, pleural cavity and intestine in steady state are positive for YFP. B cell origin of YFP+ macrophages was confirmed by next-generation sequencing of genomic DNA locus encoding immunoglobulin heavy chain genes. Eliciting a self-resolving zymosan peritonitis showed that during inflammation a subset of B-1 B cells gives rise to inflammation-induced macrophages. The aim of this study was to perform transcriptome analysis of B-1 B cell-derived macrophages (B-1/macrophages) from the naM-ove and inflamed murine peritoneum and compare them to already established populations of naM-ove tissue-resident macrophages, inflammation-experienced resident (yolk-sac-derived) macrophages and inflammation-induced (monocyte-derived) macrophages.

ORGANISM(S): Mus musculus

SUBMITTER: Dan Frampton

PROVIDER: E-MTAB-1878 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Alternatively activated macrophages derived from monocytes and tissue macrophages are phenotypically and functionally distinct

Project description:Macrophages adopt an alternatively activated phenotype (AAM) when activated by IL-4. While these AAMs can be derived from local proliferation of resident tissue macrophages or recruited inflammatory monocytes, it is not known whether these different AAMs are phenotypically and functionally distinct. Using microarray analysis of gene expression, we demonstrated that while both monocyte- and tissue-derived AAM expressed high levels of Arg1, Chi3l3 and Retnla, only monocyte-derived AAM upregulated Raldh2 and PD-L2. The distinction between monocyte- and tissue-derived macrophages can, therefore, be made using different phenotypic markers. Gene expression profiling analysis with whole genome microarray of tissue-derived and monocyte-derived macrophages, induced using IL-4c and/or 4% thioglycollate.

2014-02-05 | E-GEOD-54679 | biostudies-arrayexpress

MicroRNA expression in thioglycollate and alternatively activated

Project description:Macrophage activation must be tightly controlled to prevent overzealous responses that cause self-damage. MicroRNAs have been shown to promote classical macrophage activation by blocking concomitant anti-inflammatory signals and transcription factors, but can also place restraints on activation by preventing excessive TLR-signalling. In contrast, the microRNA profile associated with alternatively activated macrophages and their role in regulating wound-healing or anti-helminthic responses has not yet been described. Utilizing an in vivo model of alternative activation, in which adult Brugia malayi nematodes are surgically implanted in the peritoneal cavity of mice, we examined the profile of microRNA expression in these alternatively activated macrophages and compared this to alternatively activated IL-4 receptor knockout macrophages and thioglycollate elicited macrophages. Peritoneal macrophages from BALB/c wild type or IL-4 receptor knockout mice were elicited with thioglycollate or using nemtodes (peritoneal implant of Brugia malayi). The latter leads to a population of alternatively activated macrophages. Microarray analysis was used to examine the microRNA profile of WT alternatively activated macrophages (n = 4), IL-4 receptor knockout alternatively activated macrophages (n = 4), WT thioglycollate elicited macrophages (n = 3) and IL-4 receptor knockout thioglycollate elicited macrophages (n = 3).

2012-08-07 | E-GEOD-35047 | biostudies-arrayexpress

Klf4 expression in conventional dendritic cells is required for T helper 2 cell responses

Project description:Subset-specific and progenitor gene expression analysis of Klf4+/+ and Klf4-/- DCs. The two major lineages of classical dendritic cells (cDCs) express and require either IRF8 or IRF4 transcription factors for their development and function. IRF8-dependent cDCs promote anti-viral and T-helper 1 (Th1) cell responses, whereas IRF4-expressing cDCs have been implicated in controlling both Th2 and Th17 cell responses. Here, we have provided evidence that Kruppel-like factor 4 (Klf4) is required in IRF4-expressing cDCs to promote Th2 but not Th17 cell responses in vivo. Conditional Klf4 deletion within cDCs impaired Th2 cell responses during Schistosoma mansoni infection, Schistosoma egg antigen (SEA) immunization, and house dust mite challenge (HDM), without affecting cytotoxic T lymphocyte (CTL), Th1 and Th17 cell responses to herpes simplex virus, Toxoplasma gondii and Citrobacter rodentium infections. Further, Klf4 deletion reduced IRF4 expression in pre-cDCs and resulted in selective loss of IRF4-expressing cDCs subsets in several tissues. These results indicate that Klf4 guides a transcriptional program promoting IRF4-expressing cDCs heterogeneity. Bone marrow progenitors and skin draining LN subsets were harvested from 4 Klf4fl/fl cre negative or Vav1-icre mice and were sorted to >95% purity on the FACS Aria 3.

2015-05-19 | E-GEOD-68590 | biostudies-arrayexpress

RNA Sequencing of CD169+ lymph node macrophages isolated from naïve or tumor-bearing mice

Project description:CD169+ macrophages residing in naïve or tumor-draining inguinal lymph nodes revealed their protective role in tumor metastasis

2021-06-02 | E-MTAB-8482 | biostudies-arrayexpress

Transcriptomic analysis of Brugia malayi-elicited alternatively activated macrophages

Project description:RNA-Seq expression profiling of flow cytometry sorted macrophages obtained from BALB/c and IL4Ra-/- mice via thioglycollate-elicitation or Brugia malayi implantation. BALBc implanted (BNe), BALBc Thioglycollate (BTG), IL4Ra-/- implanted (KNe) and IL4Ra-/- thioglycollate (KTG) groups were prepared. Each group consists of 3 biological replicates. Each biological replicate was obtained by pooling equal masses of total RNA from 3 individual mice.

2012-11-01 | E-MTAB-995 | biostudies-arrayexpress

Transcription profiling of mouse Gr1- and Gr1+ monocytes

Project description:Six-weeks old (C57Bl6, Cx3cr1gfp/+) mice were intraperitonealy infected with a low number (1.104) of L. monocytogenes (EGDe strain) in exponential growth phase (bacteria were grown in BHI at 108/ml, and diluted 10.000x in PBS immediately before injection). Group of three mice were euthanized, before infection. Peritoneal cells were recovered by peritoneal lavage. Cells from individual mice were stained with antibodies to CD11b (PECy7), Gr1 (APC), NK1.1, B220 and CD3 (PE), and F4/80 (biotin-conjugated followed by streptavidinpacific blue) for sorting. Gr1- monocytes were purified as NK1.1- CD3- B220- CD11b+ F4/80low Gr1-, gfphigh; Gr1+ monocytes were purified as NK1.1- CD3- B220- CD11b+ F4/80low Gr1+, gfpint; and polymorphonuclear cells were purified as NK1.1- CD3- B220- CD11b+ F4/80- Gr1high, gfp-. 1.103 cells from each mice, time point, and phenotype were purified by facs sorting according to their phenotype. Samples were kept at 4°C before and during the sort. Cells were directly sorted in the SuperAmp Lysis Buffer (Miltenyi Biotec, Bergisch Gladbach, Germany) using a FACS Aria cell-sorter (BD biosciences).

2011-01-08 | E-MEXP-2545 | biostudies-arrayexpress

RNA-seq analysis of ID8 ovarian cancer cells after harvest from malignant ascites

Project description:Sequencing of mRNA from ID8 tumor cells and ID8 tumor cells harvested from ascites of mice 11 weeks after intra peritoneal inoculation show acquisition of cancer stem cell-like features in ascitic tumor cells.

2020-01-06 | E-MTAB-8140 | biostudies-arrayexpress

RNA-seq of SOX2 positive pituitary cells with and without activation of beta-catenin

Project description:RNA-sequencing of FACS sorted YFP +ve (I.e. SOX2 positive) cells from Sox2CreERT/+;R26YFP/+ (n=3) mice (control), and Sox2CreERT/+;CTNNB1lox(ex3)/+;R26YFP/+ (n=3) mice (with activation of beta-catenin).

2018-02-01 | E-MTAB-5538 | biostudies-arrayexpress

Dysregulated TLR7 signaling drives anemia via development of hemophagocytic macrophages

Project description:The debilitating autoimmune disease Systemic Lupus Erythematosus (SLE) is closely associated with Toll-like receptor (TLR) 7 and type I interferon (IFN) activity in humans and in murine SLE-like disease. Two central manifestations of SLE affect the myeloid lineage of the immune system, myeloid expansion and anemia. Yet, whether these symptoms are linked and the role of TLR7 and/or type I IFN in these processes is unclear. Here we show that TLR7 signaling promotes cell-autonomous, phosphoinositide 3-kinase (PI3K)- and mammalian target of rapamycin (mTOR)-dependent macrophage development from the common myeloid progenitor (CMP). Strikingly, this TLR7-driven macrophage development requires and is enhanced by type I IFN. Genome-wide transcriptional profiling and functional studies demonstrated that TLR7 promoted the expression of Spic, the master regulator of splenic red pulp macrophages (RPM) and preferential development of hemophagocytic RPM-like cells from CMP in vitro. We found increased incidence of RPM-like cells in vivo in a mouse model of SLE caused by TLR7 overexpression, which correlated with decreased red blood cell (RBC) count and anemia. These findings demonstrate a mechanism by which TLR7 signaling promotes anemia that is of clinical significance in SLE, other rheumatological diseases and chronic viral infections. This work also identifies a previously unknown molecular pathway by which TLR signaling and type I IFN synergize to promote myeloid development from hematopoietic progenitors. CMP were sorted from the bone marrow of wild-type C57BL/6 mice, cultured with SCF+R848 or SCFr+MCSF, and CD11b+F4/80+ macrophages sorted after 5 days, n=3 per group

2016-07-01 | E-GEOD-70520 | biostudies-arrayexpress

RNA-seq analysis of macrophages from normal and tumor-infiltrated omentum

Project description:Sequencing of mRNA from tissue-resident and tumor-associated macrophages in murine omentum display distinct transcriptional profile between macrophage subset of different origin

2020-01-06 | E-MTAB-8141 | biostudies-arrayexpress

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