Single-cell RNA transcriptomics of thymic iNKT cells from BALB/c and Cd80/Cd86 -/- (B7KO) mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE198967 | GEO | 2022/11/29
REPOSITORIES: GEO
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Project description:Single-cell TCR-seq analysis of murine thymic iNKT cells from three independent BALB/c mice and three independent Cd80/Cd86 (B7)-deficient mice
2022-11-29 | GSE198966 | GEO
Project description:Background: Traditionally, the transcriptomic and proteomic characterisation of CD4+ T cells at the single-cell level has been performed by two largely exclusive types of technologies: single-cell RNA-sequencing (scRNA-seq) and antibody-based cytometry. Here we present a multi-omics approach allowing the simultaneous targeted quantification of mRNA and protein expression in single-cells and investigate its performance to dissect the heterogeneity of human immune cell populations. Methods: We have quantified the single-cell expression of 397 genes at the mRNA level and up to 68 proteins using oligo-conjugated antibodies (AbSeq) in 43,656 primary CD4+ T cells isolated from blood and 31,907 CD45+ cells isolated from blood and matched duodenal biopsies. We explored the sensitivity of this targeted scRNA-seq approach to dissect the heterogeneity of human immune cell populations and identify trajectories of functional T-cell differentiation. Results: We provide a high-resolution map of human primary CD4+ T cells, and identify precise trajectories of Th1, Th17 and regulatory T-cell (Treg) differentiation in blood and tissue. The sensitivity provided by this multi-omics approach identified the expression of the B7 molecules CD80 and CD86 on the surface of CD4+ Tregs, and we further demonstrated that B7 expression has the potential to identify recently activated T cells in circulation. Moreover, we identified a rare subset of CCR9+ T cells in blood with gut-homing properties and expression of several immunomodulatory receptors, suggestive of a regulatory function at barrier sites. Conclusions: This transcriptomic and proteomic hybrid technology provides a cost-effective solution to dissect the heterogeneity of immune cell populations, including more precise and detailed descriptions of the differentiation and activation of circulating and tissue-resident cells in response to therapies and in stratification of patients.
2020-06-12 | GSE150060 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-11-29 | GSE198970 | GEO
Project description:Canine cutaneous histiocytoma (CCH) is a tumor originating from dermal Langerhans cells, especially affecting young dogs. The common spontaneous regression of CCH makes it an interesting model in comparative oncology research. Previous studies have indicated that anti-tumor immune responses may be involved but details remain speculative to date. Here, we asked which specific immuno-oncological dynamics underlie spontaneous regression of CCH on mRNA and protein levels. QuantSeq 3' mRNA sequencing with functional overrepresentation analysis and an nCounter RNA hybridization assay were employed on 21 formalin-fixed, paraffin-embedded CCH samples representing three different tumor stages. Nine additional samples were subjected to matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). Surprisingly, only minor stage-specific differences were found. When we investigated expression of B7 family ligands and CD28 family receptors holding co-stimulatory and -inhibitory functions respectively, we found higher abundance of CD80, CD86 and CD28, which trigger activation of lymphocyte-mediated immune responses. CD80 and CD86 expressing cells were further quantified by in situ hybridization and compared with data from three cases of canine histiocytic sarcoma (HS), a malignant tumor variant originating from antigen presenting cells. A stage-specific increase of CD80 expression was recorded in CCH from the tumor bottom to the top, while CD86 was continuously and homogenously expressed at high levels. Expression of CD80 in CCH was similar to that in HS (73.3 ± 37.4% versus 62.1 ± 46.4% positive cells), while CD86 was significantly higher expressed in CCH (94.7 ± 10.3%) when compared to HS (57.6 ± 11.0%). Our data suggest that major immuno-oncological pathways are seemingly not regulated during regression of CCH on the mRNA or protein levels as detectable by the methods used. We speculate that key signals leading to tumor regression may occur at an interactome level or at an earlier time point than examined here. Our data further supports a role of immune stimulatory B7 family ligands and CD28 family receptors in CCH regression.
2024-04-10 | GSE261395 | GEO
Project description:Canine cutaneous histiocytoma (CCH) is a tumor originating from dermal Langerhans cells, especially affecting young dogs. The common spontaneous regression of CCH makes it an interesting model in comparative oncology research. Previous studies have indicated that anti-tumor immune responses may be involved but details remain speculative to date. Here, we asked which specific immuno-oncological dynamics underlie spontaneous regression of CCH on mRNA and protein levels. QuantSeq 3' mRNA sequencing with functional overrepresentation analysis and an nCounter RNA hybridization assay were employed on 21 formalin-fixed, paraffin-embedded CCH samples representing three different tumor stages. Nine additional samples were subjected to matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). Surprisingly, only minor stage-specific differences were found. When we investigated expression of B7 family ligands and CD28 family receptors holding co-stimulatory and -inhibitory functions respectively, we found higher abundance of CD80, CD86 and CD28, which trigger activation of lymphocyte-mediated immune responses. CD80 and CD86 expressing cells were further quantified by in situ hybridization and compared with data from three cases of canine histiocytic sarcoma (HS), a malignant tumor variant originating from antigen presenting cells. A stage-specific increase of CD80 expression was recorded in CCH from the tumor bottom to the top, while CD86 was continuously and homogenously expressed at high levels. Expression of CD80 in CCH was similar to that in HS (73.3 ± 37.4% versus 62.1 ± 46.4% positive cells), while CD86 was significantly higher expressed in CCH (94.7 ± 10.3%) when compared to HS (57.6 ± 11.0%). Our data suggest that major immuno-oncological pathways are seemingly not regulated during regression of CCH on the mRNA or protein levels as detectable by the methods used. We speculate that key signals leading to tumor regression may occur at an interactome level or at an earlier time point than examined here. Our data further supports a role of immune stimulatory B7 family ligands and CD28 family receptors in CCH regression.
2024-04-10 | GSE261387 | GEO
Project description:Canine cutaneous histiocytoma (CCH) is a tumor originating from dermal Langerhans cells, especially affecting young dogs. The common spontaneous regression of CCH makes it an interesting model in comparative oncology research. Previous studies have indicated that anti-tumor immune responses may be involved but details remain speculative to date. Here, we asked which specific immuno-oncological dynamics underlie spontaneous regression of CCH on mRNA and protein levels. QuantSeq 3' mRNA sequencing with functional overrepresentation analysis and an nCounter RNA hybridization assay were employed on 21 formalin-fixed, paraffin-embedded CCH samples representing three different tumor stages. Nine additional samples were subjected to matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). Surprisingly, only minor stage-specific differences were found. When we investigated expression of B7 family ligands and CD28 family receptors holding co-stimulatory and -inhibitory functions respectively, we found higher abundance of CD80, CD86 and CD28, which trigger activation of lymphocyte-mediated immune responses. CD80 and CD86 expressing cells were further quantified by in situ hybridization and compared with data from three cases of canine histiocytic sarcoma (HS), a malignant tumor variant originating from antigen presenting cells. A stage-specific increase of CD80 expression was recorded in CCH from the tumor bottom to the top, while CD86 was continuously and homogenously expressed at high levels. Expression of CD80 in CCH was similar to that in HS (73.3 ± 37.4% versus 62.1 ± 46.4% positive cells), while CD86 was significantly higher expressed in CCH (94.7 ± 10.3%) when compared to HS (57.6 ± 11.0%). Our data suggest that major immuno-oncological pathways are seemingly not regulated during regression of CCH on the mRNA or protein levels as detectable by the methods used. We speculate that key signals leading to tumor regression may occur at an interactome level or at an earlier time point than examined here. Our data further supports a role of immune stimulatory B7 family ligands and CD28 family receptors in CCH regression. Attention: this GEO submission includes the nCounter® data from 10 of the 35 samples used in this study! The data from 3' RNA-Seq (QuantSeq 3') and the other entety-contrasting 25 tumour samples were submitted separately to GEO.
2024-03-21 | GSE262020 | GEO
Project description:Discovery of CD80 and CD86 as recent activation markers on regulatory T cells by protein-RNA single-cell analysis
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Project description:Transcriptional profiling of iNKT gene expression in Map3k1 control and mutant mice
2016-06-01 | E-MTAB-1561 | biostudies-arrayexpress
Project description:iNKT cells can be classified based on functional criteria into iNKT1, iNKT2 and iNKT17 cells, respectively. Here, a protocol was applied allowing sorting of living cells from thumus of BALB/c and C57BL/6 mice. The obtained gene expression profiles confirmed already existing information regarding the iNKT subtypes and will therefore provide useful hints for further investigations.
2016-10-05 | GSE69120 | GEO
Project description:In its more severe forms, COVID-19 progresses towards an excessive immune response, leading to the systemic overexpression of proinflammatory cytokines like IL6, mostly from the infected lungs. This cytokine storm can cause multiple organ damage and death. Consequently, there is a pressing need to identify therapies to treat and prevent severe symptoms during COVID-19. Based on previous clinical evidence, we hypothesized that inhibiting T cell co-stimulation by blocking CD80/86 could be an effective therapeutic strategy against progression to severe proinflammatory states. To support this hypothesis, we performed an analysis integrating blood transcriptional data we generated from rheumatoid arthritis patients treated with abatacept -a CD80/86 costimulation inhibitor- with the pathological features associated with COVID-19, particularly in its more severe forms. We have found that many of the biological processes that have been consistently associated with COVID-19 pathology are reversed by CD80/86 co-stimulation inhibition, including the downregulation of IL6 production. Also, analysis of previous transcriptional data from blood of SARS-CoVinfected patients showed that the response to abatacept has a very high level of antagonism to that elicited by COVID-19. Finally, analyzing a recent single cell RNA-seq dataset from bronchoalveolar lavage fluid cells from COVID-19 patients, we found a significant correlation along the main elements of the C80/86 axis: CD86+/80+ antigen presenting cells, activated CD4+ T cells and IL6 production. Our in-silico study provides additional support to the hypothesis that blocking of the CD80/CD86 signaling axis may be protective of the excessive proinflammatory state associated with COVID-19 in the lungs.
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