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Hepatic iNKT cells facilitate colorectal cancer metastasis by inducing a fibrotic niche in the liver

ABSTRACT: Hepatic iNKT cells facilitate colorectal cancer metastasis by inducing a fibrotic niche in the liver

PROVIDER: PRJNA1148410 | ENA |

REPOSITORIES: ENA

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	SRR30251492_1.fastq.gz	Fastqsanger.gz
	SRR30251492_2.fastq.gz	Fastqsanger.gz

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Hepatic iNKT cells facilitate colorectal cancer metastasis by inducing a fibrotic niche in the liver

Project description:To better understand how disseminated cancer cells activate hepatic iNKT cells, we performed single-cell RNA sequencing of NKT cells sorted from livers 24 hours after intrasplenic injection of PBS or APTKA organoids

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Extracellular Matrix Proteome of Aging-Specific Fibrotic Niche Cells in Mouse Liver Tissue

Project description:The extracellular matrix (ECM) is a complex network comprising hundreds of proteins, serving not only a structural role in shaping multicellular organisms but also participating in signaling processes. Moreover, the ECM exhibits high tissue specificity and undergoes significant alterations with aging progression. We analyzed the proteome of ECM produced by liver aging-specific fibrotic niche cells in old mice to obtain an age-related proteome profile. Our analysis revealed the identification of 714 quantifiable proteins, with 126 classified as matrisome proteins according to the matrisome database. Notably, proteins significantly upregulated in the ECM of liver aging-specific fibrotic niche cells indicated characteristics reminiscent of ECM formation (Eln, Mfap4, Lox, Tgfb2, Thbs2) and immune cell recruitment (Cxcl12), akin to those originating from fibrotic regions. Our findings suggest that this study may contribute to elucidating heightened fibrotic characteristics associated with the aging process.

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Gene expression profiling of CD244+CXCR6+ C2 iNKT cell subet and CD244-CXCR6+ C1 iNKT cell subset

Project description:We identified a novel subset of iNKT cells, C2 iNKT cells, that circulate in the periphery. Correspondingly, we characterized the tissue-resident iNKT cell subset, C1 iNKT cells. The development and terminal maturation of C2 iNKT cells completely depended on the thymic epithelial IL-15 niche, whereas C1 iNKT cells were regulated also by local IL-15 niches in peripheral tissues. C2 iNKT cells expressed high levels of genes related to cytotoxicity and exhibited more NK cell-like features. Functionally, C2 iNKT cells regulated self-antigen expression for immune tolerance in the thymus and mediated cancer immunosurveillance in the periphery.

2022-08-08 | GSE150813 | GEO

Gene expression profiling of C2, C1 and C0 iNKT cell subset

Project description:We identified a novel subset of iNKT cells, C2 iNKT cells, that circulate in the periphery. Correspondingly, we characterized the tissue-resident iNKT cell subset, C1 iNKT cells. We also found the precursor of these two subsets of iNKT cells, C0 iNKT cells in thymus. The development and terminal maturation of C2 iNKT cells completely depended on the thymic epithelial IL-15 niche, whereas C1 iNKT cells were regulated also by local IL-15 niches in peripheral tissues. C2 iNKT cells expressed high levels of genes related to cytotoxicity and exhibited more NK cell-like features. Here we characterized the C2 iNKT cells, C1 iNKT cells, and C0 iNKT cells using RNA-seq. We also performed RNA-seq for CD4+ T cells, CD8+ T cells and NK cells as a comparison. To investigate the effect of CD4, we performed the RNA-seq for the CD4+ and CD4- C2 iNKT cells.

2022-08-08 | GSE206627 | GEO

iNKT gene profiling_Map3k1

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EGFR pathway regulates the cellular interactome within the liver fibrotic niche

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Single-cell RNA-seq reveals the midkine-mediated immune microenvironment dysfunction in human keloids fibrotic niche

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Project description:Treatment of glioblastoma with anti-CSF-1R immunotherapy, radiotherapy, or surgical tumor resection were found to all induce a fibrotic response to treatment, which was highly associated with tumor recurrence. To investigate the drivers of fibrotic treatment response we performed multi-omic analysis of the glioblastoma microenvironment following treatment with anti-CSF-1R immunotherapy. Studies consisted of mass spectrometry proteomic analysis, single cell transcriptomics, and high-dimensional spatial analysis. These data identified a protective spatial niche that supported tumor cell survival following treatment, ultimately leading to tumor recurrence. Therapeutic inhibition of fibrotic treatment response blocked the formation of this niche, and significantly improved survival in anti-CSF-1R preclinical trials

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Expression data of hepatic iNKT cells from pLck-hCD1d transgenic mice

Project description:CD1d expression by thymocytes is required to select iNKT cells. When CD1d is expressed only on thymocytes (pLck-CD1d tg mice), iNKT cells are hyperresponsive to antigen stimulation suggesting that, in physiological conditions, these cells undergo functional education mediated by additional CD1d-expressing cells. Here, we investigated the mechanisms of this functional education. We find that peripheral iNKT cells from pLck-CD1d tg mice express significantly less SHP-1, a tyrosine phosphatase negatively regulating TCR signaling, than WT cells. iNKT cells from heterozygous SHP-1-mutated motheaten mice, displaying similar SHP-1 reduction as pLck-CD1d tg iNKT cells, are antigen-hyperresponsive. Restoring normal CD1d expression in pLck-CD1d tg mice normalizes SHP-1 expression and responsiveness of iNKT cells. In WT mice, iNKT cells upregulate SHP-1 and decrease responsiveness upon emigration from thymus to periphery. This depends on contacts with CD1d-expressing DCs. iNKT cell functional education is therefore controlled by DCs via tuning SHP-1 expression level in the periphery. Hepatic iNKT cells from wild-type and transgenic mice (expressing hCD1d molecule under the pLck promoter)

2013-03-01 | E-GEOD-42835 | biostudies-arrayexpress

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