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Single-cell transcriptome and TCR repertoire sequencing of cholinergic CD4+ T cells in liver cancer

ABSTRACT: ACh was originally isolated from spleen back in 1929, however, its contribution to immune regulation has only recently been appreciated. Subsets of both T and B lymphocytes have been found to express choline acetyltransferase (Chat) and produce ACh. To date, Chat-expressing T cells have been described as relaying neural signals in the spleen to modulate immune responses; regulating blood pressure; and promoting anti-viral immune responses. In a murine multi-hit model of hepatocellular carcinoma, we observed activation of the adaptive immune response and induction of Chat-expressing CD4+ T cells. These cholinergic T cells curtail the development of liver cancer by supporting anti-tumor immune responses. We used single-cell RNA sequencing to investigate the transcriptome and TCR repertoire of the Chat-expressing CD4+ T cells in healthy and HCC-bearing livers.

ORGANISM(S): Mus musculus

PROVIDER: GSE231322 | GEO | 2023/06/26

REPOSITORIES: GEO

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Transcriptome of Chat positive and negative ILC2s

Project description:Group 2 innate lymphoid cells (ILC2s) reside in multiple tissues including lymphoid organs and barrier surfaces, and secrete type 2 cytokines including interleukin (IL)-5, IL-9 and IL-13. These cells participate in multiple physiological processes including allergic inflammation, tissue repair, metabolic homeostasis and host defense against helminth infections. Recent studies indicate that neuropeptides can play an important role in regulating ILC2 responses, however, the mechanisms that underlie these processes in vivo remain incompletely defined. Here, we identify that activated ILC2s upregulate choline acetyltransferase (ChAT)—the enzyme responsible for the biosynthesis of acetylcholine (ACh)—following infection with the helminth parasite Nippostrongylus brasiliensis or treatment with alarmins or cytokines including IL-25, IL-33 and thymic stromal lymphopoietin (TSLP). ILC2s also express acetylcholine receptors (AChRs), and ACh administration promotes ILC2 cytokine production and elicits expulsion of helminth infection. In accordance with this, ChAT deficiency in ILC2s leads to defective ILC2 responses and impaired immunity against helminth infection. Together, these results reveal a previously unrecognized role of the ChAT-ACh pathway in promoting type 2 innate immunity to helminth infection.

2021-03-05 | GSE164705 | GEO

Non-neuronal acetylcholine as an endogenous regulator of proliferation and differentiation of Lgr5-positive stem cells in mice

Project description:Acetylcholine (ACh) has been considered a neurotransmitter residing in central, parasympathetic and neuromuscular synapses of mammals. Here, experiments using crypt-villus organoids that lack nerve and immune cells in culture led us to suggest that endogenous ACh is synthesized in the intestinal epithelium to evoke growth and differentiation of the organoids through activation of muscarinic ACh receptors (mAChRs). The extracts of the cultured organoids exhibit a noticeable capacity for ACh synthesis that is sensitive to a potent inhibitor of choline acetyltransferase (ChAT). Imaging mass spectrometry reveals distribution of endogenous ACh that is localized in intestinal epithelial layer in the cultured organoids as well as in mouse small intestinal epithelium in vivo, suggesting non-neural resources of ACh. Treatment of organoids with carbachol down-regulates growth of organoids and expression of marker gene for each epithelial cell. On the other hand, antagonists for mAChRs enhances growth and differentiation of organoids, indicating involvement of mAChRs in regulating proliferation and differentiation of Lgr5-positive stem cells. Collectively, our data provide evidence that endogenous ACh released from intestinal epithelium maintains homeostasis of intestinal epithelial cell growth and differentiation via mAChRs in mice. Gene expression patters of gut, crypt, y-organoid and o-organoid, respectively

2013-08-15 | E-GEOD-49864 | biostudies-arrayexpress

Lamin A/C Is Required For ChAT-Dependent Neuroblastoma Differentiation: a microarray gene expression study

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2017-04-18 | E-GEOD-73591 | biostudies-arrayexpress

Non-neuronal acetylcholine as an endogenous regulator of proliferation and differentiation of Lgr5-positive stem cells in mice

2013-08-15 | GSE49864 | GEO

Non-neuronal acetylcholine as an endogenous regulator of proliferation and differentiation of Lgr5-positive stem cells in mice

2013-08-15 | GSE49864 | GEO

Blood pressure regulation by CD4+ lymphocytes expressing choline acetyltransferase

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2016-09-12 | GSE85915 | GEO

Transcription profiling of IMR32 cells expressing 69-kDa or 82-kDa CHAT proteins

Project description:The goal of this study was to look at genes that were affected by 69-kDa and/or 82-kDa ChAT proteins in IMR32 cells Experiment Overall Design: The gene expression changes of IMR32 cells stably expressing either 69-kDa or 82-kDa ChAT proteins were anaylzed and compared to control IMR32 wild type cells. 3 biological replicates were anaylzed per condition (69-kDa ChAT expressing cells, 82-kDa ChAT expressing cells, or wild type IMR32 cells) for a total of 9 samples altogether.

2008-06-12 | E-GEOD-3506 | biostudies-arrayexpress

Kidney choline acetyltransferase (ChAT)-3

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Inhibition of p300 impairs Foxp3+ T-regulatory cell function and promotes anti-tumor immunity

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2013-08-18 | E-GEOD-47989 | biostudies-arrayexpress

Cholinergic control of Th17 cell pathogenicity in experimental autoimmune encephalomyelitis [RNA-seq]

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