The transcriptome differences between IFN-I-elicited subsets of arginase 1-high and -low macrophages
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA678291 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13055355_1.fastq.gz | Fastqsanger.gz | |||
| SRR13055355_2.fastq.gz | Fastqsanger.gz | |||
| SRR13055356_1.fastq.gz | Fastqsanger.gz | |||
| SRR13055356_2.fastq.gz | Fastqsanger.gz | |||
| SRR13055357_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 16 |
Similar Datasets
Project description:Purpose: Using cells from the Arg1-YFP reporter mice, we discovered that only a part of macrophages from IFNβ-stimulated transitional monocytes showing Arg1-YFP expression. Therefore, we probed the overall differences between such IFN-I-elicited YFP+ and YFP- macrophages. Method: Bone marrow mononuclear cells from Arg1-YFP mice were treated with M-CSF± IFNβ for 64 h. The macrophages (F4/80+) in the control and IFN treatment group were further sorted by flow cytometry based on YFP intensities. The dominant YFP- population from the control cells (Con), as well as the YFP- (Treated1) and YFP+ (Treated2) subsets within IFNβ-treated cells were subjected to RNAseq analyses. Results: The most enriched biological functions for the up-regulated genes in the treated groups relate to immune activation, anti-viral responses and the IFN pathway. Most classical IFNβ downstream genes did not display differential expression between YFP- (Treated1) and YFP+ (Treated2). However, there are 84 genes displaying “Treated2 above Treated1” and 98 genes showing “Treated1 above Treated2” patterns. Conclusions: Our result show that IFN-I-elicited YFP+ and YFP- monocyte-derived macrophages tend to be M2- and M1-skewed, respectively.
2021-06-08 | GSE161428 | GEO
Project description:Elevation of arginase enzyme activity in the lung contributes to the pathogenesis of various chronic inflammatory diseases and infections. Inhibition of arginase expression and activity is able to alleviate those effects. Here, we investigated the immunomodulatory effect of arginase inhibitor in C. neoformans infection. In the pulmonary cryptococcosis model that was shown to recapitulate human infection, we found arginase expression was excessively induced in the lung during the late stage of infection. To inhibit the activity of arginase, we administered a specific arginase inhibitor, nor-NOHA, during C. neoformans infection. Inhibition of arginase reduced eosinophil infiltration and level of IL-13 secretion in the lungs. Whole lung transcriptome RNA-sequencing analysis revealed that treatment with nor-NOHA resulted in shifting the Th2-type gene expression patterns induced by C. neoformans infection to the Th1-type immune profile, with higher expression of cytokines Ifng, Il6, Tnfa, Csf3, chemokines Cxcl9 and Cxcl10 and transcription factor Stat1. More importantly, mice treated with arginase inhibitor had more infiltrating brain leukocytes and enhanced gene expression of Th1-associated cytokines and chemokines that are known to be essential for protection against C. neoformans infection. Inhibition of arginase dramatically attenuated spleen and brain infection, with improved survival. Taken together, these studies demonstrated that inhibiting arginase activity induced by C. neoformans infection can modulate host immune response by enhancing protective type-1 immune response during C. neoformans infection. The inhibition of arginase activity could be an immunomodulatory target to enhance protective anti-cryptococcal immune responses.
2024-04-06 | GSE255160 | GEO
Project description:Muscle injury was elicited by cardiotoxin injection into the tibialis anterior muscle. Macrophages were isolated 2 days post-injury from the regenerating muscle. We used microarray to obtain global gene expression data of muscle-derived tissue macrophage subsets. Tissue macrophages were collected from regenerating muscle samples of three animals, Ly6C+ F4/80low and Ly6C- F4/80high macrophage subsets were sorted. The global gene expression patterns of distinct macrophage subsets were analyzed on Affymetrix microarrays.
2014-01-02 | E-GEOD-44057 | biostudies-arrayexpress
Project description:We compared arginase-1+ macrophages (macrophages were defined by flow cytometry as CD45hi CD11b+ Ly6G-) with arginase-1- brain macrophages following traumatic brain injury (TBI) by isolating these cells from YARG transgenic mice, which express YFP under the arginase-1 promoter. Both cell populations were isolated from YARG brain tissues one day following TBI. We also examined the expression profile of peripheral blood monocytes (monocytes were defined by flow cytometry as CD11bhi F4/80+) from injured YARG mice and from normal YARG mice. Peripheral blood samples were compared to TBI brain macrophages to assess gene expression changes before and after infiltration into the brain. TBI macrophage subsets were identified by using a reporter mouse strain (YARG) that expresses eYFP from an IRES inserted at the 3' end of the gene for arginase-1 (Arg1), a hallmark of alternatively activated (M2) macrophages. One day after TBI, 21±1.5% of ipsilateral brain macrophages expressed relatively high levels of Arg1 as detected by YFP. Gene expression analysis of Arg1+ and Arg1- brain macrophage populations revealed that these populations were distinct from either classically activated (M1) macrophages or M2 macrophages, with features of both. The Arg1+ cells differed from Arg1- cells in multiple aspects, most notably in their chemokine repertoires. Thus, the macrophage response to TBI involves recruitment of at least two major macrophage subsets. Overall, our data indicate that the macrophage response to TBI is heterogeneous and unique.
2013-05-01 | GSE39759 | GEO
Project description:Purpose: Treatment of midgestation chorionic villus explants with recombinant IFN-b leads to morphological changes including formation of syncitial knots. However, treatment of explants with IFN-l, which is constitutively expressed by syncytiotrophoblasts, is not sufficient to cause these same changes. To understand the different transcriptional changes induced by IFN-b and IFN-l and underlying cause of these morphological changes, we performed RNAsequencing after these different treatments. Methods: Chorionic villi of 18-21 gestation week placentas were dissected. Explants were cultured in DMEM F/12 with 1000 U recombinant IFN-b or 1000U recombinant IFN-l for 24 hours. RNA was then isolated from explants, and RNAsequencing was performed to assess transcriptional changes. Results/ Conclusions: IFN-b but not IFN-l induces interferon stimulated genes (ISGs) in mid gestation chorionic villus explants.
2017-12-31 | GSE104348 | GEO
Project description:Analysis of transcriptional differences after IFN-beta (IFN-b) or IFN-lambda (IFN-l) treated human mid-gestation chorionic villus explants
| PRJNA412403 | ENA
Project description:We compared arginase-1+ macrophages (macrophages were defined by flow cytometry as CD45hi CD11b+ Ly6G-) with arginase-1- brain macrophages following traumatic brain injury (TBI) by isolating these cells from YARG transgenic mice, which express YFP under the arginase-1 promoter. Both cell populations were isolated from YARG brain tissues one day following TBI. We also examined the expression profile of peripheral blood monocytes (monocytes were defined by flow cytometry as CD11bhi F4/80+) from injured YARG mice and from normal YARG mice. Peripheral blood samples were compared to TBI brain macrophages to assess gene expression changes before and after infiltration into the brain. TBI macrophage subsets were identified by using a reporter mouse strain (YARG) that expresses eYFP from an IRES inserted at the 3' end of the gene for arginase-1 (Arg1), a hallmark of alternatively activated (M2) macrophages. One day after TBI, 21±1.5% of ipsilateral brain macrophages expressed relatively high levels of Arg1 as detected by YFP. Gene expression analysis of Arg1+ and Arg1- brain macrophage populations revealed that these populations were distinct from either classically activated (M1) macrophages or M2 macrophages, with features of both. The Arg1+ cells differed from Arg1- cells in multiple aspects, most notably in their chemokine repertoires. Thus, the macrophage response to TBI involves recruitment of at least two major macrophage subsets. Overall, our data indicate that the macrophage response to TBI is heterogeneous and unique. Four groups (Arg1- brain macrophages post-TBI, Arg1+ brain macrophages post-TBI, normal blood monocytes, blood monocytes post-TBI) were analyzed. Four replicates of each group were analyzed for a total of 16 samples (only 3 replicates of the blood monocyte groups are included in this submission).
2013-05-01 | E-GEOD-39759 | biostudies-arrayexpress
Project description:Deficiency of arginase is associated with hyperargininemia, and unlike the other disorders of the urea cycle, the major mechanism of metabolism of nitrogen in terrestrial mammals, are characteristic and prominent features that include spastic diplegia/tetraplegia, clonus, and hyperreflexia; loss of ambulation, intellectual disability and progressive neurological decline are other signs. To gain greater insight into the unique neuromotor features, we performed gene expression profiling of the motor cortex of a well-characterized murine model of the disorder. Co-expression network analysis suggested an abnormality with myelination, which was supported by limited existing human data. Utilizing electron microscopy, marked dysmyelination was detected in 2-week-old homozygous ARG1 knockout mice. The corticospinal tract was found to be adversely affected, supporting dysmyelination as the cause of the unique neuromuscular features and implicating oligodendrocyte impairment in a deficiency of hepatic ARG1. Following neonatal hepatic gene therapy to express ARG1, the subcortical white matter, pyramidal tract, and corticospinal tract all showed a remarkable recovery in terms of myelinated axon density and ultrastructural integrity with active wrapping of axons by nearby oligodendrocyte processes. These findings support the following conclusions: first, arginase deficiency is a leukodystrophy affecting the brain and spinal cord while sparing the peripheral nervous system; and second, neonatal AAV hepatic gene therapy can rescue the defects associated with myelinated axons, strongly implicating the functional recovery of oligodendrocytes after restoration of hepatic arginase activity. These findings support the consideration of early restoration of hepatic arginase activity in those afflicted with arginase deficiency.
2019-06-01 | GSE132058 | GEO
Project description:Most available knowledge on fungal arginine metabolism is derived from studies on Saccharomyces cerevisiae, in which arginine catabolism is initiated by releasing urea via the arginase reaction. Orthologs of the S. cerevisiae genes encoding the first three enzymes in the arginase pathway were cloned from Kluyveromyces lactis and shown to functionally complement the corresponding deletion in S. cerevisiae. Surprisingly, deletion of the single K. lactis arginase gene KlCAR1 did not completely abolish growth on arginine as nitrogen source. Growth rate of mutant strongly increased during serial transfer in shake-flask cultures. A combination of RNAseq-based transcriptome analysis and 13C-15N-based flux analysis was used to elucidate the arginase-independent pathway. Isotopic 13C15N-enrichment in ?-aminobutyrate revealed succinate as the entry point in the TCA cycle of the alternative pathway. Transcript analysis combined with enzyme activity measurements indicated increased expression in the Klcar1? mutant of a guanidinobutyrase (EC.3.5.3.7), an enzyme not previously demonstrated in fungi. Expression of the K. lactis KLLA0F27995g (renamed KlGBU1) encoding guanidinobutyrase enabled S. cerevisiae to use guanidinobutyrate as sole nitrogen source and its deletion in K. lactis almost completely abolish growth on this nitrogen source. Phylogenetic analysis suggests that this enzyme activity is widespread in fungi. The goal of the present study was to characterize arginine catabolism in K. lactis. To this end, CAR1, CAR2 and PRO3 orthologs in K. lactis were identified and functionally analysed by deletion, expression in S. cerevisiae and enzyme activity assays. Since deletion of the arginase gene in K. lactis was found not to completely abolish growth on arginine as a sole nitrogen source, the alternative pathway for arginine catabolism operating in this yeast was studied by a combination of transcriptome analysis, 13C and 15N isotope-based flux analysis and enzyme activity assays in cell extracts. To investigate arginine metabolism in the arginase-negative K. lactis strain, strains GG1632 (Klku80? KlCAR1 reference strain) and IMS0367 (Klcar1? Arg+) were grown in aerobic bioreactor batch cultures on glucose chemically defined medium with arginine as sole nitrogen source. RNA sequencing of samples taken during the exponential phase of growth on glucose-arginine media of the reference strain G1631 and the arginase less strain IMS0367 were compared resulting in the characterization of a new function.
2014-07-16 | E-GEOD-56060 | biostudies-arrayexpress
Project description:COVID-19 ranges from asymptomatic in 35% of cases to severe in 20% of patients. Differences in the type and degree of inflammation appear to determine the severity of the disease. Recent reports show an increase in circulating monocytic-myeloid-derived suppressor cells (M-MDSC) in severe COVID 19 that deplete arginine but are not associated with respiratory complications. Our data shows that differences in the type, function and transcriptome of granulocytic-MDSC (G-MDSC) may in part explain the severity COVID-19, in particular the association with pulmonary complications. Large infiltrates by Arginase 1+ G-MDSC (Arg+G-MDSC), expressing NOX-1 and NOX-2 (important for production of reactive oxygen species) were found in the lungs of patients who died from COVID-19 complications. Increased circulating Arg+G-MDSC depleted arginine, which impaired T cell receptor and endothelial cell function. Transcriptomic signatures of G-MDSC from patients with different stages of COVID-19, revealed that asymptomatic patients had increased expression of pathways and genes associated with type I interferon (IFN), while patients with severe COVID-19 had increased expression of genes associated with arginase production, and granulocyte degranulation and function. These results suggest that asymptomatic patients develop a protective type I IFN response, while patients with severe COVID-19 have an increased inflammatory response that depletes arginine, impairs T cell and endothelial cell function, and causes extensive pulmonary damage. Therefore, inhibition of arginase-1 and/or replenishment of arginine may be important in preventing/treating severe COVID-19.
2021-06-25 | GSE178824 | GEO