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Kynurenine engages Serotonin Receptor 1b in osteoblasts to reinforce Acute Myeloid Leukemia

ABSTRACT: Kynurenine engages Serotonin Receptor 1b in osteoblasts to reinforce Acute Myeloid Leukemia

PROVIDER: PRJNA646060 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12214383_1.fastq.gz	Fastqsanger.gz
	SRR12214383_2.fastq.gz	Fastqsanger.gz
	SRR12214384_1.fastq.gz	Fastqsanger.gz
	SRR12214384_2.fastq.gz	Fastqsanger.gz
	SRR12214385_1.fastq.gz	Fastqsanger.gz

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Kynurenine engages Serotonin Receptor 1b in osteoblasts to reinforce Acute Myeloid Leukemia

Project description:We performed RNAseq analysis of primary human osteoblasts co-cultured with the human THP-1 AML cell-line and, in parallel, RNAseq analysis on the THP-1 AML cells exposed to the human primary osteoblasts.

2020-07-15 | GSE154374 | GEO

The aryl hydrocarbon receptor binds to kynurenine and mediates a signal supports the undifferentiated state in pluripotent stem cells

Project description:Kynurenine is generated from tryptophan by indoleamine 2,3-dioxygenase (IDO1) and binds to the aryl hydrocarbon receptor (AhR). We found that kynurenine generated by human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) stimulated the AhR to bind selectively to the promoters and enhancers of self-renewal genes, thus enhancing their transcription. The kynurenine-AhR complex also directly stimulated the expression of IDO1 and AHR, activating a positive feedback loop. Substantial amounts of kynurenine that were not complexed with AhR were present in the culture medium, providing a paracrine signal for maintenance of the undifferentiated state. Kynurenine was not present in the medium of differentiated ESCs and iPSCs. When cells were induced to undergo ectodermal differentiation, the abundance of kynurenine in the medium was reduced through activation of the main kynurenine catabolic pathway mediated by aminotransferase 2 (KAT2), resulting in the secretion of 2-aminoadipic acid (2-AAA) into the culture medium. Thus, kynurenine in the culture medium is a biomarker for the undifferentiated state, and 2-AAA in the culture medium is a biomarker for ESCs and iPSCs that have committed to differentiate along the ectoderm lineage.

2019-06-09 | GSE129507 | GEO

Expression Profile of Embryonic Stem Cell Derived Serotonin Neurons

Project description:The rhesus embryonic stem cell line 366.4 differentiates into serotonin neurons. RNA was extracted from ESC colonies, embryoid body (Ebs), Neurospheres in selection (N1), Proliferating serotonin neurons (N2) and differentiating serotonin neurons (N3). RNA was labeled with Enzo biotin labelling kit and hybridized to Rhesus chip from Affymetrix. single sample represent each stages and total 5 rhesus chip were hybridized

2010-04-08 | E-GEOD-16168 | biostudies-arrayexpress

Tumor-derived kynurenine induces Siglec-15 expression and promotes CD8+T cell exhaustion in oral squamous cell carcinoma

Project description:Metabolic deregulation and immune escape are pivotal hallmarks of cancer; however, the profile of metabolic reprogramming in oral squamous cell carcinoma (OSCC) and how it drives immune escape remain unclear. We identified significant metabolic disorders in OSCC. Amino acid metabolism, especially tryptophan/kynurenine metabolism, was altered. Here, we found that kynurenine promotes migration, invasion, and proliferation in vitro and in vivo. In addition, most immune checkpoints were upregulated in patients with high kynurenine levels. We then identified that kynurenine can promote Siglec-15 expression via AhR activation. Furthermore, tumor-derived kynurenine can directly exhaust CD8+ T cells, whereas blocking of kynurenine transporters reversed this effect. Moreover, we found that ectopic expression of Siglec-15 can promote immune escape in tumor microenvironment (TME) by suppressing T cell infiltration and inducing CD8+ T cell exhaustion in vivo, while targeting AhR reduces kynurenine-mediated immune escape. Finally, we design NH2-MSNs nanoparticles to deliver Siglec-15 small interfering RNA, which successfully remodels the TME and enhances anti-PD-1 efficacy in tumor-bearing immunocompetent mice. Clinically, Siglec-15 expression is correlated with AhR expression and high infiltration of exhausted CD8+ T cells. These findings reveal that the Kyn/AhR/Siglec-15 signaling pathway is a novel immunometabolism mechanism in OSCC, thus opening a new therapeutic avenue for metabolic immunotherapy.

2024-07-03 | GSE222673 | GEO

Serotonin effect on Bxpc-3 pancreatic adenocarcinoma cell line.

Project description:Analysis of Bxpc-3 cells treated with serotonin under metabolic stress induced by serum deprivation. Serotonin (5-HT), a well-known neuromodulator with both neurotransmitter and neuroendocrine functions, is also involved in tumorigenesis. Results provide insight into molecular basis of serotonin in pancreatic cancer.

2016-05-12 | GSE81355 | GEO

Kynurenine treatment of herpesivrus stimulated iCD103 dendritic cells

Project description:We report the gene expression (obtained by next generation RNAseq) of inducible CD103+ dendritic cells, iCD103 cells, stimulated with both murine herpesvirus-68 and the immunomodulatory tryptophan derivative kynurenine (kyn). This study provides data on how tryptophan derivatives can modulate pro-inflammatory cytokine expression in virus treated dendritic cells.

2021-01-01 | GSE160307 | GEO

Expression Profile of Embryonic Stem Cell Derived Serotonin Neurons

2009-05-21 | GSE16168 | GEO

MED12 mutation activates the tryptophan/kynurenine/AHR pathway to promote growth of uterine leiomyomas

Project description:Uterine leiomyoma (LM) is the most common tumor in women. Estrogen and progesterone, via their receptors ERα and PR, play essential roles in LM growth. Mediator complex subunit 12 (MED12) mutations occur in 70% of all LM and are thought to drive tumor growth in a steroid hormone-dependent manner; however, the mechanisms remain unclear. Here, we performed ChIP-seq (ERα, PR, and MED12) and RNA-seq on LM expressing mutant MED12 (mut-MED12) or wild-type MED12 and matched myometrium. Mut-MED12 altered PR and chromatin interaction landscapes, with significant PR-binding site loss in proximal promoter regions in mut-MED12 LM. Integration of cistrome and transcriptome data identified tryptophan 2,3-dioxygenase (TDO2) as a PR and MED12 target gene, which was aberrantly upregulated in mut-MED12 LM. Kynurenine, the catabolic product of TDO2, was significantly elevated in mut-MED12 LM. Tryptophan or kynurenine treatment of primary LM cells activated the aryl hydrocarbon receptor (AHR) pathway, increased cell proliferation, and inhibited apoptosis; blocking the TDO2-kynurenine-AHR pathway by siRNA knockdown or pharmacologic inhibition abolished these effects. Mut-MED12 LM cells showed higher sensitivity to these treatments. These findings suggest that activation of the TDO2-kynurenine-AHR pathway in mut-MED12 LM induces tumor growth, and may inform the development of targeted treatments and precision medicine in LM.

2023-05-01 | GSE204968 | GEO

Plasma kynurenine mediated pathological communication between gut microbiota and ventricular remodeling in children with pressure overload

Project description:Abnormally elevated plasma kynurenine (Kyn) was detected in the patient cohort and single nuclues sequecing revealed its molecular role

2023-07-19 | GSE210833 | GEO

Cancer anorexia: the role of serotonin in hypothalamic resistance of the neuropeptide Y system [A358_GEO_hypocells]

Project description:Anorexia is a common symptom among cancer patients and contributes to malnutrition and insufficient food intake. In cancer-induced anorexia, food intake regulation in the hypothalamus appears to be impaired. A negative energy balance persists and accelerates muscle wasting and malnutrition. Moreover, it strongly affects mortality and survival in these patients. Here, we show that the neuropeptide Y system (NPY) appears to fail to respond adequately to changes in energy balance during cancer cachexia. In addition, we investigate the connection between serotonin and NPY release in hypothalamic cell lines. Hypothalamic neuronal cells mHypoE-46 (serotonin sensitive cells) and mHypoA-2/12 (serotonin unresponsive cells) were used to study the effect of serotonin on messenger NPY expression and NPY excretion.

2014-10-31 | E-GEOD-57189 | biostudies-arrayexpress

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