Ontology highlight
ABSTRACT:
PROVIDER: PRJNA839893 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19329400.fastq.gz | Fastqsanger.gz | |||
| SRR19329401.fastq.gz | Fastqsanger.gz | |||
| SRR19329386.fastq.gz | Fastqsanger.gz | |||
| SRR19329387.fastq.gz | Fastqsanger.gz | |||
| SRR19329388.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 16 |
Similar Datasets
Project description:The lactate receptor GPR81 contributes to cancer development, yet the mechanisms remain unclear. Here, we show that GPR81 is upregulated in human cancers and further upregulated by extracellular lactate and three-dimensional growth of breast cancer spheroids. GPR81 knockdown (KD) increased spheroid necrosis and reduced invasion and in vivo tumor growth. GPR81 KD altered GO terms relating to extracellular matrix (ECM) and cell adhesion, including upregulation of Protocadherin-7 (PCDH7), which exhibited a striking, clustered expression in spheroids. Single cell analysis revealed that PCDH7 was inversely related with Ki-67 and co-clustered with other GPR81 KD-upregulated genes including Ephrin-type-A receptor-7 (EPHA7). The matricellular protein SPARC and the Notch ligand Delta-like-4 (DLL4), were downregulated upon GPR81 KD, and their KD elicited spheroid necrosis (DLL4) and inhibited invasion. We conclude that GPR81 supports breast cancer aggressiveness at least in part via SPARC and DLL4. Our findings substantiate GPR81 as a promising target in breast cancer treatment.
2022-05-23 | GSE203441 | GEO
Project description:Coronaries are essential for myocardial growth and heart function. Notch is crucial for mouse embryonic angiogenesis, but its role in coronary development remains uncertain. We show Jag1, Dll4 and activated Notch1 receptor expression in sinus venosus (SV) endocardium. Endocardial Jag1 removal blocks SV capillary sprouting, while Dll4 inactivation stimulates excessive capillary growth, suggesting that ligand antagonism regulates coronary primary plexus formation. Later endothelial ligand removal, or forced expression of Dll4 or the glycosyltransferase MFng, blocks coronary plexus remodeling, arterial differentiation, and perivascular cell maturation. Endocardial deletion of Efnb2 phenocopies the coronary arterial defects of Notch mutants. Angiogenic rescue experiments in ventricular explants, or in primary human endothelial cells, indicate that EphrinB2 is a critical effector of antagonistic Dll4 and Jag1 functions in arterial morphogenesis. Thus, coronary arterial precursors are specified in the SV prior to primary coronary plexus formation and subsequent arterial differentiation depends on a Dll4-Jag1-EphrinB2 signaling cascade.
2019-12-03 | GSE110614 | GEO
Project description:Dll4-Notch signaling is required for cell fate decisions and neoplasias. However, emerging evidence suggests a role for Dll4-Notch signaling in metabolic and immune diseases. To date, there is no evidence of a direct effect of Dll4-Notch signaling inhibition on pancreatic islet function and insulin secretion.
2018-08-13 | PXD005333 | Pride
Project description:Interactions between acute myeloid leukemia (AML) and the bone marrow microenvironment (BMME) are critical to leukemia progression and chemoresistance. In the solid tumor microenvironment, altered metabolite levels contribute to cancer progression. We performed a metabolomic analysis of AML patient bone marrow serum, revealing increased metabolites compared to age- and sex-matched controls. The most highly elevated metabolite in the AML BMME was lactate. Lactate signaling in solid tumors induces immunosuppressive tumor-associated macrophages and correlates with poor prognosis. This has not yet been studied in the leukemic BMME. Herein, we describe the role of lactate in the polarization of leukemia-associated macrophages (LAMs). Using a murine AML model of blast crisis chronic myelogenous leukemia (bcCML), we characterize the suppressive phenotype of LAMs by surface markers, transcriptomics, and cytokine profiling. Then, mice genetically lacking GPR81, the extracellular lactate receptor, were used to demonstrate GPR81 signaling as a mechanism of both the polarization of LAMs and the direct support of leukemia cells. Furthermore, elevated lactate diminished the function of hematopoietic progenitors and reduced stromal support for normal hematopoiesis. We report microenvironmental lactate as a mechanism of AML-induced immunosuppression and leukemic progression, thus identifying GPR81 signaling as an exciting and novel therapeutic target for treating this devastating disease.
2026-03-11 | GSE313457 | GEO
Project description:Hypoxia (low oxygen) and Notch signaling are two important regulators of vascular development, but how they interact in controlling the choice between arterial and venous fates for endothelial cells during vasculogenesis is less well understood. In this report, we show that hypoxia and Notch signaling intersect in promotion of arterial differentiation. Hypoxia upregulated expression of the Notch ligand Dll4 and increases Notch signaling, in a process requiring the vasoactive hormone adrenomedullin but not endogenous VEGF. Notch signaling also upregulated Dll4 expression, leading to a positive feedback loop sustaining Dll4 expression and Notch signaling. In addition, functional Notch signaling was required for hypoxia to upregulate the arterial marker genes Depp, connexin40 (Gja5), Cxcr4 and Hey1. In conclusion, the data reveal an intricate interaction between hypoxia and Notch signaling in the control of endothelial cell differentiation, including a hypoxia/adrenomedullin/Dll4 axis that initiates Notch signaling and a requirement for Notch signaling to effectuate hypoxiamediated induction of the arterial differentiation program.
2013-02-08 | GSE35894 | GEO
Project description:Identification of Notch ligand useage by splenic B cells using Dll1 and Dll4 Notch ligand blockade.
| PRJNA1148919 | ENA
Project description:Skeletal muscle aging is associated with increased lipid accumulation, or myosteatosis, leading to lipotoxicity and loss of muscle function. Here, we report that loss of the novel lactate receptor GPR81 in aged muscle is associated with impaired lipid oxidation and enhanced lipid accumulation. Knockdown of GPR81 in young healthy myoblasts led to an increase in senescence hallmarks such as DNA damage, accumulation of reactive oxygen species (ROS), mitochondrial dysfunction and impaired autophagy. Conversely, treatment of senescent myoblasts with GPR81 agonists enhanced lipid oxidation in senescent myoblasts leading to a decrease in lipid accumulation, ultimately resulting in decreased DNA damage, ROS accumulation and enhanced ability to form myotubes. In agreement with our in vitro findings, we observed significant improvement in muscle regeneration and overall health of aged or progeric mice that were treated with GPR81 agonists. Our findings suggest that GPR81 plays a key role in skeletal muscle lipid metabolism, and agonists of GPR81 might play a promising role in reversing age-associated lipid accumulation and loss of muscle function.
2026-06-01 | GSE325224 | GEO
Project description:The Notch pathway is a major regulator of endothelial transcriptional specification. Targeting the Notch receptors or the ligand Dll4 dysregulates angiogenesis. Here, by analyzing single and compound genetic mutants for all Notch signaling members, we find significant differences in the way ligands and receptors regulate liver vascular homeostasis. Loss of Notch receptors caused endothelial hypermitogenic cell-cycle arrest and senescence. Conversely, Dll4 loss triggered a strong Myc-driven transcriptional switch, inducing endothelial proliferation and the tip-cell state. Myc loss suppressed the induction of angiogenesis in the absence of Dll4, without preventing the vascular enlargement and organ pathology. Similarly, inhibition of other pro-angiogenic pathways, including MAPK/ERK and mTor, had no effect on the vascular expansion induced by Dll4 loss; however, anti-VEGFA treatment prevented it without fully suppressing the transcriptional and metabolic programs. This study shows incongruence between single-cell transcriptional states, vascular phenotypes, and related pathophysiology. Our findings also suggest that vascular structure abnormalization, rather than neoplasms, causes the reported anti-Dll4 antibody toxicity.
2023-05-12 | GSE231612 | GEO
Project description:In hESCs, expression of the Notch ligand DLL4 parallels the emergence of bipotent hematoendothelial progenitors (HEPs) and promotes their hematopoietic differentiation. During differentiation, DLL4 is only expressed in a subpopulation of HEPs. To study the developmental fate of the two subpopulations of HEPs identified by DLL4 expression, we FACS-isolated DLL4high and DLL4low/- HEPs at day 15 of differentiation and performed gene expression analysis using microarrays
2014-05-01 | GSE56881 | GEO
Project description:Hypoxia (low oxygen) and Notch signaling are two important regulators of vascular development, but how they interact in controlling the choice between arterial and venous fates for endothelial cells during vasculogenesis is less well understood. In this report, we show that hypoxia and Notch signaling intersect in promotion of arterial differentiation. Hypoxia upregulated expression of the Notch ligand Dll4 and increases Notch signaling, in a process requiring the vasoactive hormone adrenomedullin but not endogenous VEGF. Notch signaling also upregulated Dll4 expression, leading to a positive feedback loop sustaining Dll4 expression and Notch signaling. In addition, functional Notch signaling was required for hypoxia to upregulate the arterial marker genes Depp, connexin40 (Gja5), Cxcr4 and Hey1. In conclusion, the data reveal an intricate interaction between hypoxia and Notch signaling in the control of endothelial cell differentiation, including a hypoxia/adrenomedullin/Dll4 axis that initiates Notch signaling and a requirement for Notch signaling to effectuate hypoxiamediated induction of the arterial differentiation program. 12 microarray samples consisting of >50,000 FACS sorted CD31+ cells purified from wild type mouse CCE ES cells that were differentiated into the endothelial lineages in 3 biological replicates. The ES cells were subjected to embryoid body formation over 4 days in hanging drop cultures, FACS sorted for Flk1 positive vascular progenitors cells and plated for a further 4 days in normoxia (21% oxygen) or hypoxia (1.5-2% oxygen) with or without 4 umol/l gamma-secretase inhibitor L-685.458.
2013-02-08 | E-GEOD-35894 | biostudies-arrayexpress