Similar Datasets
Project description:Hippocampal gene expression from Nr2f1 heterozygous knockout and WT mice
| PRJNA416215 | ENA
Project description:The nuclear receptor Nr2f1 acts as a strong transcriptional regulator in embryonic and postnatal neural cells. In humans, its mutations cause the Bosch-Boonstra-Schaaf optic atrophy-intellectual syndrome (BBSOAS), a rare neurodevelopmental disorder characterized by multiple clinical features including optic nerve atrophy, intellectual disability, and autistic traits. In this study, by genome-wide and in silico analyses we identified a wide set of nuclear-encoded mitochondrial genes as potential genomic targets under direct Nr2f1 transcriptional control in neurons. By combining mouse genetics, neuroanatomical and imaging approaches we demonstrated that conditional Nr2f1 loss-of-function within the adult mouse hippocampal neurogenic niche results in a reduced mitochondrial mass associated with mitochondrial fragmentation and downregulation of key mitochondrial proteins in newborn neurons, whose functional integration and survival are impaired. Importantly, we also found dysregulation of several mitochondrial genes and downregulation in levels of key mitochondrial proteins in the brain of mice heterozygous for Nr2f1, a validated BBSOAS model. Our data point to an active role of Nr2f1 in the mitochondrial gene expression regulatory network in neurons and support the involvement of mitochondrial dysfunction in BBSOAS pathogenesis.
2023-06-09 | GSE228566 | GEO
Project description:Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) has been identified as an autosomal-dominant disorder characterized by a complex neurological phenotype, with high prevalence of intellectual disability and optic nerve atrophy/hypoplasia. The syndrome is caused by loss-of-function mutations in NR2F1, which encodes a highly conserved nuclear receptor that serves as a transcriptional regulator. Previous investigations to understand the protein's role in neurodevelopment have mostly used mouse models with constitutive and tissue-specific homozygous knockout of Nr2f1. In order to represent the human disease more accurately, which is caused by heterozygous NR2F1 mutations, we investigated a heterozygous knockout mouse model and found that this model recapitulates some of the neurological phenotypes of BBSOAS, including altered learning/memory, hearing defects, neonatal hypotonia and decreased hippocampal volume. The mice showed altered fear memory, and further electrophysiological investigation in hippocampal slices revealed significantly reduced long-term potentiation and long-term depression. These results suggest that a deficit or alteration in hippocampal synaptic plasticity may contribute to the intellectual disability frequently seen in BBSOAS. RNA-sequencing (RNA-Seq) analysis revealed significant differential gene expression in the adult Nr2f1+/- hippocampus, including the up-regulation of multiple matrix metalloproteases, which are known to be critical for the development and the plasticity of the nervous system. Taken together, our studies highlight the important role of Nr2f1 in neurodevelopment. The discovery of impaired hippocampal synaptic plasticity in the heterozygous mouse model sheds light on the pathophysiology of altered memory and cognitive function in BBSOAS.
| S-EPMC7104670 | biostudies-literature
Project description:Long non-coding RNA NR2F1 antisense RNA1 (lncRNA NR2F1-AS1) was identified as the main candidate associated to late recurrence in ER-positive breast cancer clinical samples. Gain-of-function of NR2F1-AS1 induced the expression of dormancy-inducers BMP4 and DEC2, and upregulated pluripotency markers NANOG and OCT4. Representative pathways entailed to metastatic events such as HER2/Neu, hypoxia, EMT and inflammatory-response were also found enriched.
2019-12-31 | GSE128600 | GEO
Project description:Long non-coding RNA NR2F1 antisense RNA1 (lncRNA NR2F1-AS1) was identified as the main candidate associated to late recurrence in ER-positive breast cancer clinical samples. Gain-of-function of NR2F1-AS1 induced the expression of dormancy-inducers BMP4 and DEC2, and upregulated pluripotency markers NANOG and OCT4. Representative pathways entailed to metastatic events such as HER2/Neu, hypoxia, EMT and inflammatory-response were also found enriched.
2019-12-31 | GSE128617 | GEO
Project description:Periphilin is a protein which is involved in multiple processes in vivo, including terminal differentiation of keratinozytes as well as cell-cycle and cancer related functions. Here we generated mice with a targeted disruption of the periphilin-1 gene to explore its physiological role from an organismic perspective. In accordance with a ubiquitous expression of periphilin in the murine embryo, the homozygous deficiency of periphilin is lethal in early embryogenesis. We therefore characterized mice with a disruption of only one periphilin allele. As heterozygous periphilin knockout mice show no obvious histological alterations and have no apparent behavioural phenotypes, we compared whole transcriptome RNA expression profiles of total brain tissue of periphilin+/- knockout mice and wild type littermates for an in-depth analysis of heterozygous animals. In periphilin+/- knockout mice, 3 probe sets were indicative of significant differential expression (p ≤ 0.05, SLR ≥ 1 which is equivalent to 2 fold). Two of these probe sets (1438864_at and 1439170_at) refer to unannotated or unclassifiable genes. According to the NetAffx™ Analysis Center, the third probe set (1447831_s_at) is assigned to myotubularin related protein 7 (Mtmr7). The probe set, however, lies upstream of the Mtmr7 gene (Ensembl gene ENSMUSG00000039431), and its signal is therefore not representative for the Mtmr7 gene. Quantitative RT-PCR (qRT-PCR) analysis with a primer set specific for Mtmr7 confirmed that its expression is not altered in periphilin+/- knockout mice (relative expression compared to wild type: 0.924; p = 0.419). In summary, none of more than 45.000 covered transcripts is differentially expressed in periphilin+/- knockout mice in comparison to wild type littermates.
2009-04-01 | GSE14059 | GEO
Project description:We considered the possibility that removal of E2F4, as a key regulator of cellular quiescence, would cause systemic perturbations in the expression of E2F4 bound genes involved in cell cycle and proliferation. To test whether these pertubrations were reflected in the adult tissues' gene expression programs, we compared the gene expression profile of E2F4 double knockout mice to the gene expression found in identical tissues from E2F4 heterozygous littermates, that are phenotypically normal. We selected liver, testes, and kidney to profile by gene expression analysis, because two of these tissues are affected at some point during development when E2F4 is missing.
2007-06-14 | E-MEXP-1131 | biostudies-arrayexpress
Project description:We show that the epithelial-like and mesenchymal-like subpopulations of breast cancer stem-like cells (BCSCs) demonstrate different levels dormancy and tumorigenicity in lungs. The long non-coding RNA (lncRNA) molecule NR2F1-AS1 (NAS1) is up-regulated in the dormant BCSC subpopulation, and functionally promotes tumor dissemination but reduces proliferation in lungs. Mechanically, NAS1 promotes internal ribosome entry site (IRES)-mediated NR2F1 translation, leading to inhibition of ΔNp63 transcription by NR2F1. Further, ΔNp63 downregulation results in epithelial-mesenchymal transition, reduced tumorigenicity and enhanced dormancy of cancer cells in lungs.
2023-04-23 | GSE149265 | GEO
Project description:Our data showed that NR2F1-AS1 functions oncogenic roles in gastric cancer (GC), but the underlying molecular mechanism remains largely unknown to date. To explore the function of lncRNA NR2F1-AS1 in gastric cancer, loss-of-function and RNA sequencing studies were performed in SGC7901 cell line. The results showed that depletion of NR2F1-AS1 significantly decreased the expression of VAMP7. Interestingly, VAMP7 was also a target gene of miR-29a-3p. Our data showed that NR2F1-AS1 promotes GC progression through regulating miR-29a/VAMP7 axis.
2021-10-07 | GSE183538 | GEO
Project description:To investigate the mechanism of NPR1 regulating vascular function, we established NPR1 knockout heterozygous mice by CRISPR-Cas9. We performed high-throughput RNA sequencing to analyse the transcriptom of the aorta of NPR1 knocout heterogeneous mice.
2022-10-14 | GSE215215 | GEO