Gene changes associated with deletion of Esrrg in spiny projection neurons in mice using RNA sequencing
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE198214 | GEO | 2025/03/01
REPOSITORIES: GEO
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Project description:Purpose: The goal of this study is to understand what gene changes are associated with removal of Esrrg in dopaminerigc neurons from the mouse midbrain using BAC-TRAP and an AAV for Thcre Methods: Midbrain from mice expressing the L10a transgene used for BAC-TRAP method of RNA isolation both with and without deletion of Esrrg using AAV:THCre were aged 1 month post-injection and midbrains were then extracted and flash frozen on dry ice. RNA was isolated using the BAC-TRAP method and samples were sent for sequencing.
2022-08-22 | GSE198216 | GEO
Project description:Purpose: The goal of this study is to understand what gene changes are associated with removal of Esrrg in parvalbumin-positive neurons from the mouse cortex using BAC-TRAP Methods: Cortex from mice expressing the L10a transgene used for BAC-TRAP method of RNA isolation and PVcre on either WT or ESRRG flox backgrounds, 3-4 monts of age; two hemispheres/mouse were then extracted and flash frozen on dry ice. RNA was isolated using the BAC-TRAP method and samples were sent for sequencing.
2025-03-01 | GSE198213 | GEO
Project description:Striato nigral circuit is composed of medium spiny neuronal projections that were mainly sent from striatum to midbrain substantial nigra (SN), which is essential for regulating motor behaviors. Dysfunction of striato-nigral circuitry may cause a series of motor disabilities which are associated with neurodegenerative disorders, such as Huntington disease (HD). Although the etiology of HD is known as abnormally expanded CAG repeats of the huntingtin gene (HTT), treatment of HD remains tremendous challenges. One possible reason is lack of effective HD model which resembles striato nigral circuitry deficits for the pharmacology studies. Here we first differentiate striatum-like organoids from human pluripotent stem cells, containing functional medium spiny neurons (MSN). We then generated 3D striato nigral circuitoids by assembling striatum-like organoids with midbrain substantial nigra like organoids. With AVV hSYN GFP viral tracing, the extensive MSN projections from striatum to SN are established, which form synaptic connection with dopaminergic neurons and showed the electronic field potentials by labeling striatum like organoids with optogenetic virus. Furthermore, this striato nigral circuitoids exhibited improved calcium activity than individual striatal organoids. Importantly, we further demonstrated the reciprocal projection defects of the HD iPSC derived circuitoids, which could be reversed with the treatment of brain derived nerve factors. Altogether, the striato nigral circuitoids could be used for identifying MSN projection defects, which would be applied as a potential drug test platform for HD.
2024-05-06 | GSE251684 | GEO
Project description:PM2.5 exposure is closely linked to the exacerbation of asthma. Estrogen related receptor gamma (Esrrg), an orphan nuclear receptor, exerts a crucial role as a transcription factor in various metabolic diseases. Nevertheless, the impacts of Esrrg on PM2.5-triggered asthma aggravation have not been investigated. Herein, ovalbumin (OVA)-induced asthmatic mice were exposed to PM2.5 to establish a mouse model of asthma aggravation by PM2.5. In view of mRNA sequencing, Esrrg was the only member of nuclear receptor superfamily in the up-regulated differentially expressed genes in OVA compared with Naive groups as well as OVA+PM2.5 compared with OVA groups (|log2 (fold change)|>1 and p<0.05). In vivo, adeno-associated virus carrying Esrrg shRNA (AAV-shEsrrg) was applied to silencing Esrrg. In addition, Esrrg activity was suppressed pharmacologically with an inverse agonist GSK5182. Either AAV-shEsrrg or GSK5182 ameliorated airway inflammation in the PM2.5-aggravated asthmatic mice. In vitro, isolated mouse primary tracheobronchial epithelial cells (MTEC) from mice were identified by detecting cytokeratin 7-positive cells. The treatment of adenovirus vector with shEsrrg or GSK5182 mitigated the cell damage induced by PM2.5. Notably, phosphodiesterase 3B (Pde3b) expression was declined by Esrrg inhibition in vivo and in vitro. Dual luciferase reporter and ChIP-PCR assays showed the binding of Esrrg to the Pde3b promoter. Taken together, these results revealed that Esrrg inhibition alleviated airway inflammation in the PM2.5-deteriorated asthmatic mouse model and prevented PM2.5-driven MTEC injury through binding to the Pde3b promoter, which might contribute to further study the therapy of PM2.5-aggravated asthma.
2025-01-13 | GSE286089 | GEO
Project description:L-3,4-dihydroxyphenylalanine (levodopa) treatment is the major pharmacotherapy for Parkinson's disease. However, almost all patients receiving levodopa eventually develop debilitating involuntary movements (dyskinesia). While it is known that striatal spiny projection neurons (SPNs) are involved in the genesis of this movement disorder, the molecular basis of dyskinesia is not understood. In this study, we identify distinct cell-type-specific gene expression changes that occur in sub-classes of SPNs upon induction of a parkinsonian lesion followed by chronic levodopa treatment. We identify several hundred genes whose expression is correlated with levodopa dose, many of which are under the control of AP-1 and ERK signaling. In spite of homeostatic adaptations involving several signaling modulators, AP-1-dependent gene expression remains highly dysregulated in direct pathway SPNs (dSPNs) upon chronic levodopa treatment. We also discuss which molecular pathways are most likely to dampen abnormal dopaminoceptive signaling in spiny projection neurons, hence providing potential targets for antidyskinetic treatments in Parkinson's disease. To profile the cell-type-specific responses of striatal spiny projection neurons (SPNs) to striatal dopamine depletion, we conducted TRAP analysis of the two major classes of these neurons: dSPNs that express the dopamine receptor 1a (Drd1a), and iSPNs that express the dopamine receptor 2 (Drd2). To disrupt dopamine innervation to both of these SPN populations that reside in the striatum, we injected the neurotoxin 6-hydroxydopamine (6-OHDA), unilaterally, in the medial forebrain bundle (MFB) in hemizygous Drd1-TRAP and Drd2-TRAP adult (9-14 weeks) male mice (kept on a C57BL/6J genetic background). This lesion procedure causes nigral dopamine cell death within a few days, along with a widespread and near-complete loss of dopaminergic innervation to the entire dorsal striatum on one side of the brain (a hemiparkinsonian model). We first examined the effects of dopamine depletion alone, compared to a mock lesion (ascorbate / saline injected). We then examined the effects of chronic levodopa treatment upon the molecular profiles of dopamine- depleted dSPNs and iSPNs, with two dose regimens. The ‘high-dose’ L-DOPA regimen (3 mg/kg on days 1-3, followed by 6 mg/kg on days 4-9) was expected to induce severe dyskinesia in all MFB-lesioned mice. The low-dose L-DOPA regimen (1 mg/kg on days 1-3, followed by 2 mg/kg on days 4-9) was expected to reverse limb use asymmetry without causing conspicuous dyskinesias. To equalize the effects of stress and handling across all groups, including control groups, all mice were equally handled and thus received saline injections when not receiving levodopa injections. Each treatment group contained 7-10 replicates. TRAP-purified mRNAs from either Drd1a- or Drd2-expressing SPNs were reverse-transcribed, amplified, and used to interrogate Affymetrix 430_2.0 GeneChip microarrays.
2014-03-03 | E-GEOD-55096 | biostudies-arrayexpress
Project description:ESRRG is one of nuclear receptor super family. ESRRG contributes to many physiological pathway. Especially, ESRRG is clearly involved in various cancers. To identify the downstream target of ESRRG in gastric cancer, we carried out microarray.
2019-12-03 | GSE78050 | GEO
Project description:Retinoblastoma (Rb) is a deadly childhood eye cancer that is classically initiated by inactivation of the RB1 tumor suppressor. Clinical management continues to rely on nonspecific chemotherapeutic agents that are associated with treatment resistance and toxicity. Here, we analyzed 103 whole exomes, 16 whole transcriptomes, 5 single-cell transcriptomes, and 4 whole genomes from primary Rb tumors to identify novel Rb dependencies. Several recurrent genomic aberrations implicate estrogen-related receptor gamma (ESRRG) in Rb pathogenesis. RB1 directly interacts with and inhibits ESRRG, and RB1 loss uncouples ESRRG from negative regulation. ESRRG regulates genes involved in retinogenesis and oxygen metabolism in Rb cells. ESRRG is preferentially expressed in hypoxic Rb cells in vivo. Depletion or inhibition of ESRRG causes marked Rb cell death which is exacerbated in hypoxia. These findings reveal a novel dependency of Rb cells on ESRRG, and they implicate ESRRG as a potential therapeutic vulnerability in Rb.
2022-08-24 | GSE196420 | GEO
Project description:Long-range glutamatergic inputs from the cortex and thalamus provide important motor and cognitive information to the striatum where they are integrated for learning and action planning. Genetic programs and transcription factors that orchestrate the development of these inputs are relatively unknown. The transcription factor, FOXP1, is crucial for the development of spiny projection neurons (SPNs) in the striatum. We investigated the cell-specific role of Foxp1 in the formation of glutamatergic inputs – including corticostriatal inputs. Embryonic Foxp1 deletion in dopamine receptor 2-expressing SPNs (D2 Foxp1cKO) leads to reduced transmission of corticostriatal excitatory inputs and decreased synaptically driven excitability. Postnatal deletion of Foxp1 also resulted in decreased glutamatergic inputs onto D2 SPNs. Single nuclei RNA sequencing of D2 Foxp1cKO striatum identified downregulated postsynaptic genes, consistent with the synaptic phenotype. Reinstating Foxp1 postnatally rescued electrophysiological deficits and expression of a subset of genes that were altered by embryonic deletion in D2 SPNs. Postnatal Foxp1 reinstatement could also rescue behavioral phenotypes. In summary, we demonstrate that FOXP1 regulates the development of corticostriatal circuitry. Further, changes at multiple levels of brain function resulting from loss of Foxp1 are rescued with postnatal Foxp1 reinstatement, indicating a therapeutic approach for individuals with FOXP1 syndrome.
2024-02-20 | GSE243662 | GEO
Project description:To understand the developing striatum, key genes during development were identified using microarray analsyis tha could be considered as marker of medium spiny neurons. The ages studied is at peak striatal neurogenesis. 3 different gestational ages of CD1 mice were used with triplicate repeats
2016-06-23 | E-GEOD-55497 | biostudies-arrayexpress
Project description:To investigate insight into how Esrrg regulates the TREG transcriptional program, we performed high-throughput RNA sequencing (RNA-seq) analysis of CD4+Foxp3-YFP+ from splenic cells of WT and KO female mice (2-3 months old). We show that the Esrrg-deficient Treg cells presented increased transcript related to oxidative phosphoration, cell cycle, proteasome, and antigen-presenting, suggesting Esrrg plays an essential role in mitochondral metabolism and it is associated with antigen-presenting and processing. Finally, Esrrg-deficient Treg displayed decreased Erbb and ribosome pathway, which may also related to TREG function. Our data suggest an critical role of lupus susceptibility gene Esrrg in regulating Treg cell function through mitochondrial metabolism.
2020-09-01 | GSE150187 | GEO