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ABSTRACT:
PROVIDER: PRJNA1135232 | ENA |
REPOSITORIES: ENA
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Project description:An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes [P28]
| PRJNA1161421 | ENA
Project description:Establishing tools that can target and manipulate specific neuronal populations is critical to understanding neural circuits and developing targeted therapies. Recombinant adeno-associated virus (rAAV) is a popular tool for gene delivery and is widely used in basic research as well as gene therapy. Significant effort has been made to develop rAAV tools that can drive cell-type or tissue specific transgene expression. One of the strategies to develop such tools is to incorporate cell-type specific enhancer elements into the rAAV genome. In recent years, we and others have identified a number of enhancers that, when incorporated into rAAV vectors, can restrict the transgene expression to particular neuronal populations. Yet, viral tools to access and manipulate fine neuronal subtypes are still limited. Here, we performed systematic analysis of single cell ATAC-seq and RNA-seq data to identify enhancer candidates for each of the cortical interneuron subtypes.We established a set of enhancer-AAV tools that are highly specific for distinct cortical interneuron populations and striatal cholinergic neurons. These enhancers, when used in the context of different effectors, can target (fluorescent proteins), observe activity (gCaMP) and manipulate (opto- or chemo-genetics) specific neuronal subtypes. We also validated our enhancer-AAV tools across species. Thus, we provide the field with a powerful set of tools to study neural circuits and functions and to develop precise and targeted therapy.
2025-05-21 | GSE272181 | GEO
Project description:Establishing tools that can target and manipulate specific neuronal populations is critical to understanding neural circuits and developing targeted therapies. Recombinant adeno-associated virus (rAAV) is a popular tool for gene delivery and is widely used in basic research as well as gene therapy. Significant effort has been made to develop rAAV tools that can drive cell-type or tissue specific transgene expression. One of the strategies to develop such tools is to incorporate cell-type specific enhancer elements into the rAAV genome. In recent years, we and others have identified a number of enhancers that, when incorporated into rAAV vectors, can restrict the transgene expression to particular neuronal populations. Yet, viral tools to access and manipulate fine neuronal subtypes are still limited. Here, we performed systematic analysis of single cell ATAC-seq and RNA-seq data to identify enhancer candidates for each of the cortical interneuron subtypes.We established a set of enhancer-AAV tools that are highly specific for distinct cortical interneuron populations and striatal cholinergic neurons. These enhancers, when used in the context of different effectors, can target (fluorescent proteins), observe activity (gCaMP) and manipulate (opto- or chemo-genetics) specific neuronal subtypes. We also validated our enhancer-AAV tools across species. Thus, we provide the field with a powerful set of tools to study neural circuits and functions and to develop precise and targeted therapy.
2025-05-21 | GSE277242 | GEO
Project description:Cortical interneuron (CIN) dysfunction is thought to play a major role in neuropsychiatric conditions like epilepsy, schizophrenia and autism. It is therefore essential to understand how the development, physiology and functions of CINs influence cortical circuit activity and behavior in model organisms such as mice and primates. We sought to discover gene regulatory enhancer elements (REs) that can be used in AAV viral vectors to drive expression in CINs through systematic genome-wide identification of putative REs (pREs) that are preferentially active in immature CINs by histone modification ChIP-seq. We evaluated two novel pREs in AAV vectors, alongside the well-established Dlx I12b enhancer, and found that they drove CIN-specific reporter expression in adult mice.
2020-09-24 | GSE158428 | GEO
Project description:Using Sst and parvalbumin subtype-specific fluorescence activated cell sorting (FACS) and RNA sequencing we identify distinct transcriptome profiles for these interneuron subtypes in the medial PFC. Chronic stress causes significant dysregulation of several key pathways, including sex specific differences in the SST interneuron profiles.
2019-10-10 | GSE138670 | GEO
Project description:Nkx2.2, Nkx6.1, and Olig2 are transcriptional repressors regulating somatic motor neuron and interneuron subtypes in neural progenitors. The purpose of this study was to identify their target genes and to elucidate their gene regulatory mechanisms, including their relationship to Sonic Hedgehog/Gli pathway.
2015-08-24 | GSE61673 | GEO
Project description:GABAergic interneuron in the cortex comprise a very heterogenous group. and it is critical to identify discrete interneuron types to understand how their contributions to behavior can be modulated by external and internal cues. However, molecular difinition of these interneuron cell groups has been difficult. Comparative analysis of different interneuron subtypes can provide us new candidate marker genes which could target more specific interneu?on cell group. Here we identify oxytocin responsive novel class of interneuron through our comparative analysis. We employed the bacTRAP strategy, which uses BAC transgenic mice expressing EGFP-tagged ribosomal protein L10a in specific cell populations, to affinity purify polysome-bound mRNAs from Nek7, Dlx1, Cort, Htr3a, Oxtr expressing cortical interneurons. We show that Oxtr expressing cells are a subtype of somatostatin positive interneurons. Three independent TRAP replicates were collected and total RNA from the immunoprecipitates or flow-through (input) whole cortex lysates were amplified and hybridized. Data were normalized with the GCRMA algorithm and replicates were averaged across conditions. We recommend filtering data to remove probe sets with normalized expression values less than 50 in at least one condition. Because the Nek7 BAC labels non-neuronal cells, we recommend to delete astrocytes and oligodendrocytes genes from the list using GSE13379 data.
2014-10-07 | E-GEOD-56996 | biostudies-arrayexpress
Project description:Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic and refractory disease, characterized by necrotizing small to medium vessel vasculitides. AAV constitutes three distinct disorders: microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) (formerly known as Wegener's granulomatosis), and eosinophilic granulomatosis with polyangiitis (EGPA) (formerly known as Churg-Strauss syndrome). ANCA, a characteristic autoantibody for AAV consists of two major subtypes: one against myeloperoxidase (MPO-ANCA) and the other against leukocyte proteinase 3 (PR3-ANCA). MPO-ANCA is mainly detected in patients with MPA (55-90%) and in those with EGPA (20-40%) and less frequently detected in patients with GPA (20-30%). We hypothesized that an aberrant PTM occurred in neutrophil MPO in patients with MPO-ANCA-positive AAV (MPO-AAV) is involved in the production of MPO-ANCA. To test the hypothesis, SWATH-MS was used to comprehensively quantify PTMs of human MPO purified from neutrophils of MPO-AAV and healthy controls, and PTMs of mouse MPO treated with hydrogen peroxide in vitro.
2025-04-21 | PXD050920 | Pride
Project description:GABAergic interneuron in the cortex comprise a very heterogenous group. and it is critical to identify discrete interneuron types to understand how their contributions to behavior can be modulated by external and internal cues. However, molecular difinition of these interneuron cell groups has been difficult. Comparative analysis of different interneuron subtypes can provide us new candidate marker genes which could target more specific interneuｒon cell group. Here we identify oxytocin responsive novel class of interneuron through our comparative analysis. We employed the bacTRAP strategy, which uses BAC transgenic mice expressing EGFP-tagged ribosomal protein L10a in specific cell populations, to affinity purify polysome-bound mRNAs from Nek7, Dlx1, Cort, Htr3a, Oxtr expressing cortical interneurons. We show that Oxtr expressing cells are a subtype of somatostatin positive interneurons.
2014-10-07 | GSE56996 | GEO
Project description:Methylation of lysine4 on Histone H3 (H3K4) is require for promoter and enhancer activation at gene loci and presents distinct methylation patterns over developmental gene clusters. Disrupting in the writer, eraser and reader of H3K4 methylation is associated with developmental syndromes. However, less studies focus on the role of H3K4 methylation in development of interneuron and hypothalamus. Here, we explore the role of H3K4 methylation in the medial ganglionic eminence (MGE) derive interneuron and hypothalamus by directly mutating the lysine 4 on H3.3 to the methionine in mice.
2025-07-14 | GSE293655 | GEO