Prox1 in VIP interneurons
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB37790 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR4027210.fastq.gz | Fastqsanger.gz | |||
| ERR4027220.fastq.gz | Fastqsanger.gz | |||
| ERR4027211.fastq.gz | Fastqsanger.gz | |||
| ERR4027221.fastq.gz | Fastqsanger.gz | |||
| ERR4027212.fastq.gz | Fastqsanger.gz |
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Project description:Autism spectrum disorders (ASDs) are a neurodevelopmental disorder characterized by impairments in social interactions and stereotyped behaviors. While ASD has a strong genetic background, environmental factors including toxins, pesticides, infection and drugs are also known to confer autism susceptibility, likely by inducing epigenetic changes. Exposure to Valproic acid (VPA), a drug for epilepsy and bipolar disorders, during pregnancy is highly associated with the risk of ASD children. In rodents, in utero VPA exposure can precipitate behavioral phenotypes related to ASD in the offspring. Since VPA is an inhibitor of histone deacethytransferase (HDAC) activity, it thought to cause ASD with epigenetic modification. However, the core mechanism by which prenatal VPA exposure causes onset of ASD is still not fully uncovered. Here we revealed that prenatal VPA exposure strongly influences development of vasoactive intestinal peptide (VIP) - positive neurons, a subtype of cortical GABAergic interneurons. The number of VIP+ interneurons was severely reduced in somatosensory area of VPA-exposed ASD animals. We then found that the reduction in VIP+ interneurons is caused by the inhibition of HDAC3 activity upon prenatal VPA exposure. Importantly, prenatal HDAC3 inhibition caused not only the selective reduction in VIP+ interneurons but also the ASD-like behaviors in mice. We then demonstrated that the HDAC3 inhibition aberrantly activates Notch signaling, which influences the cell fate determination of VIP+ interneuron progenitors in caudal ganglionic eminence. Thus, this study uncovers the mechanism by which specific HDAC inhibition during development influences a specific type of GABAergic interneurons in the ASD model. The findings provide a novel insight into the understanding of ASD pathophysiology.
2022-06-20 | GSE133932 | GEO
Project description:In our study, we investigated the effect of Vasoactive intestinal peptide (VIP) on murine intestinal stem cell (ISC) activity and differentiation in homeostatic conditions and following irradiation-induced injury. We utilized a model of murine intestinal organoids and observed that VIP promotes epithelial differentiation towards a secretory phenotype predominantly via the p38 MAPK pathway. Moreover, VIP prominently modulates epithelial proliferation as well as the number and proliferative activity of Lgr5-EGFP+ ISC under homeostatic conditions. Further analysis revealed that in vitro acute irradiation injury renders Lgr5-EGFP+ ISC even more susceptible to modulations by VIP, which results in the strong promotion of epithelial regeneration by VIP. Finally, these effects by VIP translate into an in vivo model of abdominal irradiation, where VIP was shown to prominently mitigate radiation-induced injury. Taken together, our findings indicate a prominent role of VIP in modulating ISC behavior in intestinal homeostasis and its potential to promote intestinal regeneration following acute irradiation injury.
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Project description:Analysis of CGTH-W-1 follicular thyroid carcinoma cells transcriptome following 48 hrs siRNA-mediated depletion of PROX1. PROX1 is a homeobox transcription factor. PROX1 depletion decreases migratory ability, motility and invasivness and induces profound cytoskeleton changes of CGTH-W-1 cells. Results provide insight into the role of PROX1 in the thyroid cancer. Three biological replicates for a given condition
2016-07-31 | E-GEOD-80135 | biostudies-arrayexpress
Project description:Identification of the Early Vasoactive Intestinal Peptide (VIP) Transriptome and its Associated Interactome in Activated Murine CD4 T Cells In an attempt to understand the biological role of this neuropeptide in the immune system, we choose CD4 T cells as a cellular system for identifying a VIP-induced transcriptome. Murine CD4 T cells were isolated and used to identify changes in gene expression in the presence of PMA/ionomycin (activated) for five hours with and without 10-7 M VIP. Balanced-block design, 6 biological replicates. PMA/ionomycin (activated) mouse CD4 T spleenocytes with VIP ligand (sample) vs. PMA/ionomycin (activated) mouse CD4 T spleenocytes without VIP ligand (control), dye-swaps.
2010-01-09 | E-GEOD-18525 | biostudies-arrayexpress
Project description:Identification of the Early Vasoactive Intestinal Peptide (VIP) Transriptome and its Associated Interactome in Resting Murine CD4 T Cells In an attempt to understand the biological role of this neuropeptide in the immune system, we choose CD4 T cells as a cellular system for identifying a VIP-induced transcriptome. Murine CD4 T cells were isolated and used to identify changes in gene expression in the absence of PMA/ionomycin (resting) with and without 10-7 M VIP. Balanced-block design, 6 biological replicates. Naïve mouse CD4 T spleenocytes with VIP ligand (sample) vs. naïve mouse CD4 T spleenocytes without VIP ligand (control), dye-swaps.
2010-01-09 | E-GEOD-18524 | biostudies-arrayexpress
Project description:Accumulation of excess nutrients hampers proper liver function and is linked to non-alcoholic fatty liver disease (NAFLD) in obesity. However, the signals responsible for an impaired adaptation of hepatocytes to obesogenic dietary cues remain still largely unknown. Post-translational modification by the Small Ubiquitin-like Modifier (SUMO), allows for adynamic regulation of numerous processes including transcriptional reprograming. We demonstrate that specific SUMOylation of transcription factor Prox1 represents a nutrient-sensitive determinant of hepatic fasting metabolism. Prox1 was highly SUMOylated on lysine 556 in the liver of ad libitum and re-fed mice, while this modification was abolished upon fasting. In the context of diet-induced obesity, Prox1 SUMOylation became less sensitive to fasting cues. The hepatocyte-selective knock-in of a SUMOylation-deficient Prox1 mutant into mice fed a high-fat/high-fructose diet led to a reduction of systemic cholesterol levels, associated with the induction of liver bile acid detoxifying pathways during fasting. The generation of tools to maintain the nutrient-sensitive SUMO-switch on Prox1 may thus contribute to the development of “fasting-based” approaches for the preservation of metabolic health.
2023-10-24 | PXD041329 | Pride
Project description:Cell fate plasticity enables development, yet unlocked plasticity is a cancer hallmark. Regulating cell identity requires gene activation and repression. While master regulators induce lineage-specific genes to restrict plasticity, it remains unclear whether unwanted plasticity is actively suppressed by lineage-specific repressors. Here, we computationally predict so-called safeguard repressors for 18 cell types that block phenotypic plasticity lifelong. We validated hepatocyte-specific candidates using reprogramming, revealing that Prospero homeobox protein 1 (PROX1) enhanced hepatocyte identity by direct repression of alternate fate master regulators. In line with patient data, PROX1 overexpression in mice blocked initiation and progression of hepatocellular carcinoma and extended survival. Remarkably, Prox1 depletion caused hepatocyte fate loss in vitro, and promoted transdifferentiation of hepatocellular- to cholangio-carcinoma in vivo. Our findings provide mechanistic evidence for PROX1 as a hepatocyte-specific safeguard and support a model where individual cell type-specific repressors actively suppress plasticity throughout life to safeguard lineage choice and prevent disease.
2024-11-11 | PXD053043 | Pride
Project description:Cell fate plasticity enables development, yet unlocked plasticity is a cancer hallmark. While transcription master regulators induce lineage-specific genes to restrict plasticity, it remains unclear whether plasticity is actively suppressed by lineage-specific repressors. Here, we computationally predict so-called safeguard repressors for 18 cell types that block phenotypic plasticity lifelong. We validated hepatocyte-specific candidates using reprogramming, revealing that Prospero homeobox protein 1 (PROX1) enhanced hepatocyte identity by direct repression of alternative fate master regulators. In mice, Prox1 was required for efficient hepatocyte regeneration after injury and was sufficient to prevent liver tumorigenesis. In line with patient data, Prox1 depletion caused hepatocyte fate loss in vivo and enabled the transition of hepatocellular carcinoma to cholangiocarcinoma. Conversely, overexpression promoted cholangiocarcinoma to hepatocellular carcinoma transdifferentiation. Our findings provide evidence for PROX1 as a hepatocyte-specific safeguard and support a model where cell type-specific repressors actively suppress plasticity throughout life to safeguard lineage identity and thus prevent disease.
2024-12-18 | GSE224829 | GEO
Project description:Cell fate plasticity enables development, yet unlocked plasticity is a cancer hallmark. While transcription master regulators induce lineage-specific genes to restrict plasticity, it remains unclear whether plasticity is actively suppressed by lineage-specific repressors. Here, we computationally predict so-called safeguard repressors for 18 cell types that block phenotypic plasticity lifelong. We validated hepatocyte-specific candidates using reprogramming, revealing that Prospero homeobox protein 1 (PROX1) enhanced hepatocyte identity by direct repression of alternative fate master regulators. In mice, Prox1 was required for efficient hepatocyte regeneration after injury and was sufficient to prevent liver tumorigenesis. In line with patient data, Prox1 depletion caused hepatocyte fate loss in vivo and enabled the transition of hepatocellular carcinoma to cholangiocarcinoma. Conversely, overexpression promoted cholangiocarcinoma to hepatocellular carcinoma transdifferentiation. Our findings provide evidence for PROX1 as a hepatocyte-specific safeguard and support a model where cell type-specific repressors actively suppress plasticity throughout life to safeguard lineage identity and thus prevent disease.
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Project description:Cell fate plasticity enables development, yet unlocked plasticity is a cancer hallmark. While transcription master regulators induce lineage-specific genes to restrict plasticity, it remains unclear whether plasticity is actively suppressed by lineage-specific repressors. Here, we computationally predict so-called safeguard repressors for 18 cell types that block phenotypic plasticity lifelong. We validated hepatocyte-specific candidates using reprogramming, revealing that Prospero homeobox protein 1 (PROX1) enhanced hepatocyte identity by direct repression of alternative fate master regulators. In mice, Prox1 was required for efficient hepatocyte regeneration after injury and was sufficient to prevent liver tumorigenesis. In line with patient data, Prox1 depletion caused hepatocyte fate loss in vivo and enabled the transition of hepatocellular carcinoma to cholangiocarcinoma. Conversely, overexpression promoted cholangiocarcinoma to hepatocellular carcinoma transdifferentiation. Our findings provide evidence for PROX1 as a hepatocyte-specific safeguard and support a model where cell type-specific repressors actively suppress plasticity throughout life to safeguard lineage identity and thus prevent disease.
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