This work was conducted to identify shared and specific target genes of different ETS transcription factor rearrangements in prostate cancer. Potential target genes were identified by differential gene expression analysis of primary tumor samples with ETS rearrangements, and validated by ETS silencing in prostate cancer cell lines.
Molecular subtyping of primary prostate cancer reveals specific and shared target genes of different ETS rearrangements.
Specimen part
View SamplesAging is a major risk factor for many neurological pathologies, including Alzheimer's disease (AD). However, the mechanisms underlying brain aging and cognitive decline remain elusive. Body tissues are perfused by interstitial fluid (ISF), which is locally reabsorbed via the lymphatic vascular network. In contrast, the parenchyma of the central nervous system (CNS) is devoid of lymphatic vasculature; in the brain, removal of cellular debris and toxic molecules, such as amyloid beta (A?) peptides, is mediated by a combination of transcellular mechanisms of transport across the blood-brain and blood-cerebrospinal fluid (CSF) barriers, phagocytosis and digestion by resident microglia and recruited monocytes/macrophages, and CSF influx and ISF efflux through a paravascular route. The recent characterization of meningeal lymphatic vessels prompted a reassessment of the conventional pathways of CNS waste clearance. The role of this vasculature in brain function, specifically in the context of aging and AD, is still poorly understood. Here we show that meningeal lymphatic vessels play an essential role in maintaining brain homeostasis by draining macromolecules from the CNS (CSF and ISF) into the cervical lymph nodes. Using pharmacological, surgical, and genetic models we show that impairment of meningeal lymphatic function in adult mice slows paravascular influx of CSF macromolecules and efflux of ISF macromolecules, and induces cognitive impairment. Treatment with a lymphangiogenic factor, vascular endothelial growth factor C (VEGF-C), enhances meningeal lymphatic drainage of CSF macromolecules, improving brain perfusion and learning and memory performance in aged mice. Disruption of meningeal lymphatic vessels in transgenic mouse models of AD promotes amyloid deposition in the meninges, which closely correlates with human meningeal pathology, and aggravates overall disease severity. Our findings suggest that meningeal lymphatic dysfunction may be an aggravating factor in AD pathology and in age-associated cognitive decline. Thus, augmentation of meningeal lymphatic function might be a promising therapeutic target for preventing or delaying age-associated neurological diseases. Overall design: Male C57BL/6J mice (2 months-old) were injected (intra-cisterna magna) with Visudyne (verteporfin for injection), or vehicle as control, and submitted to a step of photoconversion, to induce meningeal lymphatic vessel ablation. This procedure was repeated 2 weeks later to ensure prolonged meningeal lymphatic dysfunction. 2 weeks after the last surgical procedure, mice were subjected to the MWM test. 3 days after, whole hippocampus was macrodissected and total RNA was extracted for sequencing.
Functional aspects of meningeal lymphatics in ageing and Alzheimer's disease.
Age, Specimen part, Cell line, Treatment, Subject
View SamplesAging is a major risk factor for many neurological pathologies, including Alzheimer's disease (AD). However, the mechanisms underlying brain aging and cognitive decline remain elusive. Body tissues are perfused by interstitial fluid (ISF), which is locally reabsorbed via the lymphatic vascular network. In contrast, the parenchyma of the central nervous system (CNS) is devoid of lymphatic vasculature; in the brain, removal of cellular debris and toxic molecules, such as amyloid beta (A?) peptides, is mediated by a combination of transcellular mechanisms of transport across the blood-brain and blood-cerebrospinal fluid (CSF) barriers, phagocytosis and digestion by resident microglia and recruited monocytes/macrophages, and CSF influx and ISF efflux through a paravascular route. The recent characterization of meningeal lymphatic vessels prompted a reassessment of the conventional pathways of CNS waste clearance. The role of this vasculature in brain function, specifically in the context of aging and AD, is still poorly understood. Here we show that meningeal lymphatic vessels play an essential role in maintaining brain homeostasis by draining macromolecules from the CNS (CSF and ISF) into the cervical lymph nodes. Using pharmacological, surgical, and genetic models we show that impairment of meningeal lymphatic function in adult mice slows paravascular influx of CSF macromolecules and efflux of ISF macromolecules, and induces cognitive impairment. Treatment with a lymphangiogenic factor, vascular endothelial growth factor C (VEGF-C), enhances meningeal lymphatic drainage of CSF macromolecules, improving brain perfusion and learning and memory performance in aged mice. Disruption of meningeal lymphatic vessels in transgenic mouse models of AD promotes amyloid deposition in the meninges, which closely correlates with human meningeal pathology, and aggravates overall disease severity. Our findings suggest that meningeal lymphatic dysfunction may be an aggravating factor in AD pathology and in age-associated cognitive decline. Thus, augmentation of meningeal lymphatic function might be a promising therapeutic target for preventing or delaying age-associated neurological diseases. Overall design: Male C57BL/6J mice (2 months-old) were injected (intra-cisterna magna) with Visudyne (verteporfin for injection), or vehicle as control, and submitted to a step of photoconversion, to induce meningeal lymphatic vessel ablation. This procedure was repeated 2 weeks later to ensure prolonged meningeal lymphatic dysfunction. 2 weeks after the last surgical procedure, whole hippocampus was macrodissected and total RNA was extracted for sequencing.
Functional aspects of meningeal lymphatics in ageing and Alzheimer's disease.
Age, Specimen part, Cell line, Treatment, Subject
View SamplesAging is a major risk factor for many neurological pathologies, including Alzheimer's disease (AD). However, the mechanisms underlying brain aging and cognitive decline remain elusive. Body tissues are perfused by interstitial fluid (ISF), which is locally reabsorbed via the lymphatic vascular network. In contrast, the parenchyma of the central nervous system (CNS) is devoid of lymphatic vasculature; in the brain, removal of cellular debris and toxic molecules, such as amyloid beta (A?) peptides, is mediated by a combination of transcellular mechanisms of transport across the blood-brain and blood-cerebrospinal fluid (CSF) barriers, phagocytosis and digestion by resident microglia and recruited monocytes/macrophages, and CSF influx and ISF efflux through a paravascular route. The recent characterization of meningeal lymphatic vessels prompted a reassessment of the conventional pathways of CNS waste clearance. The role of this vasculature in brain function, specifically in the context of aging and AD, is still poorly understood. Here we show that meningeal lymphatic vessels play an essential role in maintaining brain homeostasis by draining macromolecules from the CNS (CSF and ISF) into the cervical lymph nodes. Using pharmacological, surgical, and genetic models we show that impairment of meningeal lymphatic function in adult mice slows paravascular influx of CSF macromolecules and efflux of ISF macromolecules, and induces cognitive impairment. Treatment with a lymphangiogenic factor, vascular endothelial growth factor C (VEGF-C), enhances meningeal lymphatic drainage of CSF macromolecules, improving brain perfusion and learning and memory performance in aged mice. Disruption of meningeal lymphatic vessels in transgenic mouse models of AD promotes amyloid deposition in the meninges, which closely correlates with human meningeal pathology, and aggravates overall disease severity. Our findings suggest that meningeal lymphatic dysfunction may be an aggravating factor in AD pathology and in age-associated cognitive decline. Thus, augmentation of meningeal lymphatic function might be a promising therapeutic target for preventing or delaying age-associated neurological diseases. Overall design: Lymphatic endothelial cells (LECs) were isolated from meninges of adult (2-3 months-old) or old (20-24 months-old) male C57BL/6 mice. Cells were sorted by FACS according to the following phenotype: CD45-CD31+PDPN+.
Functional aspects of meningeal lymphatics in ageing and Alzheimer's disease.
Specimen part, Cell line, Subject
View SamplesTo evaluate the effect of IGF2BPs on mRNA stability and gene expression output, we conducted RNA-seq in individual IGF2BP knockdown and control HepG2 cells with or without actinomycin D treatment. Our RNA-seq and RNA stability profiling revealed that IGF2BPs were involved in RNA stability regulation and contributed to the stabilization of the transcriptome. Overall design: HepG2 cells were infected with individual lentiviral IGF2BP shRNA and non-specific control (shNS), and selected by puromycin to generate stable knockdown lines. We treated HepG2 cells with actinomycin D to inhibit transcription and collected cells at indicated time points (i.e., 0h, 1h, 3h, 6h). The total RNA was extracted by miRNeasy Kit (Qiagen) and sequenced by Illumina. For IGF2BP-dependent gene expression, untreated cells (i.e., 0h samples) were sequenced in triplicate and analyzed. For RNA stability profiling, RNA half-life was calculated by comparing the gene expression at 1, 3, 6 hours with actinomycin treatment to that in un-treated samples, with two biological replicates for each group.
Recognition of RNA N<sup>6</sup>-methyladenosine by IGF2BP proteins enhances mRNA stability and translation.
Specimen part, Treatment, Subject, Time
View SamplesCharacterization of differential gene expression due to cisplatin resistance in human ovarian cancer spheroids by microarray analysis.
Cisplatin Resistant Spheroids Model Clinically Relevant Survival Mechanisms in Ovarian Tumors.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Pluripotency-related, valproic acid (VPA)-induced genome-wide histone H3 lysine 9 (H3K9) acetylation patterns in embryonic stem cells.
Specimen part, Cell line, Treatment, Time
View SamplesGene expression profiles of E14 embryonic stem cells (ESCs) before and after treatment with low levels of the histone deacetylase (HDAC) inhibitors valproic acid (VPA) and sodium butyrate (NaBu).
Pluripotency-related, valproic acid (VPA)-induced genome-wide histone H3 lysine 9 (H3K9) acetylation patterns in embryonic stem cells.
Specimen part, Cell line, Treatment
View SamplesGene expression profiles of E14 embryonic stem cells (ESCs) before and after treatment with low levels of the histone deacetylase (HDAC) inhibitor valproic acid (VPA).
Pluripotency-related, valproic acid (VPA)-induced genome-wide histone H3 lysine 9 (H3K9) acetylation patterns in embryonic stem cells.
Specimen part, Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptome and metabolome analysis of liver and kidneys of rats chronically fed NK603 Roundup-tolerant genetically modified maize.
Sex, Specimen part
View Samples