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Single-cell RNA-seq analysis of the T-cell lymphoproliferative and inflammatory disorders triggered by defective LAT signalosome

ABSTRACT: Single-cell RNA-seq analysis of the T-cell lymphoproliferative and inflammatory disorders triggered by defective LAT signalosome

PROVIDER: PRJNA787596 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17183714.fastq.gz	Fastqsanger.gz
	SRR17183715.fastq.gz	Fastqsanger.gz
	SRR17183716.fastq.gz	Fastqsanger.gz

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Single-cell RNA-seq analysis of the lymphoproliferative disorders triggered by defective LAT signalosome. Modulation of the pathology in the context of two additional mutations, Stat6KO or Grap2KO

Project description:LatY136F mice in which tyrosine 136 of the LAT adaptor is mutate accumulate CD4+ T cells that trigger a fast-onset autoimmune and inflammatory condition called LAT signaling pathology (LSP). Its histopathological manifestations resemble those of human IgG4-related disease (IgG4-RD), an inflammatory condition unifying a constellation of clinical entities leading to multi-organ damage. LatY136F mice deprived of STAT6 transcription factor develop a lymphoproliferative disorder with a kinetics and magnitude identical to that of LatY136F mice. Consistent with a role of STAT6 in Th2 differentiation, the LatY136F x Stat6KO lymphoproliferative disorder is characterize by a lymphoproliferation of both CD4 and CD8 Tc producing high levels of IFN-g. This Tc proliferation is associated with massive B cell proliferation and hyperglobulinemia G2a and G2b. Using single-cell RNA sequencing, we analyzed 48287 CD4 and CD8 T cells isolated from the spleen of LatY136F and LatY136F x Stat6KO mice over the period that leads to LSP installation. In this study, LatY136F lymphoproliferative disorder is also analyze in Grab2KO mice. Unexpectedly, LatY136F x Grap2KO mice present a lymphoproliferative disorder similar to the one observed in LatY136F mice but this time TCRgd Tc.

2022-11-30 | GSE210453 | GEO

Single-cell RNA-seq analysis of the T-cell lymphoproliferative and inflammatory disorders triggered by defective LAT signalosome

Project description:LatY136F mice in which tyrosine 136 of the LAT adaptor is mutated accumulate CD4+ T cells that trigger a fast-onset autoimmune and inflammatory condition called LAT signaling pathology (LSP). Its histopathological manifestations resemble those of human IgG4-related disease (IgG4-RD), an inflammatory condition unifying a constellation of clinical entities leading to multi-organ damage. Using single-cell RNA sequencing, we analyzed 5,030 CD4+ T cells isolated from the spleen of LatY136F mice over the period that leads to LSP installation. It charted the trajectory leading to full-fledged LSP and demonstrated that LSP involved T follicular helper (Tfh) cells, CD4+ cytotoxic T cells, and IgG1+ plasma cells. These cell types were also identified in the massive infiltrates found in LatY136F lung. Therefore, the LatY136F LSP entails all the cell types postulated to trigger human IgG4-RD. It offers the unique possibility to disentangle their pathological cross-talk as illustrated here using B cell-deficient LatY136F mice.

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Single-cell RNA-seq analysis of the lymphoproliferative disorders triggered by defective LAT signalosome. Modulation of the pathology in the context of two additional mutations, Stat6KO or Grap2KO

Project description:Single-cell RNA-seq analysis of the lymphoproliferative disorders triggered by defective LAT signalosome. Modulation of the pathology in the context of two additional mutations, Stat6KO or Grap2KO

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Quantitative proteomics analysis of signalosome dynamics in primary T cells identifies the surface receptor CD6 as a Lat adaptor-independent TCR signaling hub

Project description:The aim of the dataset was to study on a genome-wide level the impact of Lat deficiency on gene expression in resting and activated CD4+ T cells Lat+ and Lat? CD4+ T cells were isolated from lymph nodes and spleen of Latfl-dtr Tmat-Cre mice using a Dynabeads untouched mouse CD4 cells kit (Life Technology) and further purified by cell sorting. Lat+ CD4+ T cells were defined as: CD5+, hDTR+, CD8?, TCR???, CD25?, CD69?, CD62L+, lineage (CD11c, CD11b, CD19, CD45R, CD161)? and Lat? CD4+ Tcells were defined as: CD5+, hDTR?, CD8?, TCR???, CD25?, CD69?, CD62L+, lineage (CD11c, CD11b, CD19, CD45R, CD161)?. Sorted Lat+ or Lat? CD4+ T cells were then kept in vitro for 4 hours without stimulation or activated for 4 hours using anti-CD3 antibody and anti-CD28 antibody. Cell samples corresponding to three biological replicates were analyzed and gene expression profiles were obtained from total RNA.

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Quantitative proteomics analysis of signalosome dynamics in primary T cells identifies the surface receptor CD6 as a Lat adaptor-independent TCR signaling hub

Project description:The aim of the dataset was to study on a genome-wide level the impact of Lat deficiency on gene expression in resting and activated CD4+ T cells

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