Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-programmable cell type monitoring and manipulation in the human cortex with CellREADR

ABSTRACT: Reliable and systematic access to diverse cell types is necessary for understanding the organization, function, and pathophysiology of human neural circuits. Methods for targeting human neural populations are scarce and currently center on identifying transcriptional enhancers and engineering viral capsids. Here we demonstrate the utility of CellREADR, a programmable RNA sensor-effector technology that couples cellular RNA sensing to effector protein translation, for accessing, monitoring, and manipulating specific neuron types in human cortex, ex vivo. We designed CellREADRs to target two subpopulations, CALB2 GABAergic interneurons and FOXP2 glutamatergic projection neurons, then validated targeting specificity using histological, electrophysiological, and transcriptomic methods. CellREADR expression of channelrhodopsin and GCamp enabled the manipulation and monitoring of these populations in live cortical microcircuits. By demonstrating specific, reliable, and programmable experimental access to human neuronal subpopulations, our results highlight CellREADR’s potential for studying neural circuits and treating brain disorders.

ORGANISM(S): Homo sapiens

PROVIDER: GSE299596 | GEO | 2025/06/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes

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

An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes [P28]

2025-05-21 | GSE277242 | GEO

Axonal and somatodendritic proteomes of dopamine neurons in the mouse brain

Project description:Dopamine (DA) neurons modulate neural circuits and behaviors via dopamine release from expansive, long range axonal projections. The elaborate cytoarchitecture of DA neurons is embedded within complex brain tissues, making it difficult to access the DA neuronal proteome using conventional methods. Here, we demonstrate APEX2 proximity labeling within genetically targeted neurons in the mouse brain, enabling subcellular proteomics with cell type-specificity. By combining APEX2 biotinylation with mass spectrometry, we mapped the somatodendritic and axonal proteomes of DA neurons. Our dataset reveals the proteomic architecture underlying axonal transport, dopamine transmission, and axonal metabolism in DA neurons. We find a significant enrichment of proteins encoded by Parkinson’s disease-linked genes in dopaminergic axons, including proteins with previously undescribed axonal localization. Our proteomic datasets comprise a significant resource for axonal and DA neuronal cell biology, while the methodology developed here will enable future studies of other neural cell types.

2021-06-01 | PXD026229 | Pride

Optogenetic neural stem cells microarray

Project description:We elucidate the transcriptome effects of optogenetics on developing neural stem cells population. The application of optogenetics in neural stem cell (NSC), allow photo-modulation of NSC in an activity-dependent manner. This provided spatio-temporal tool for studying activity dependent neurogenesis, including the potential of regulating the differentiation and maturation process of transplanted NSC. Currently, this is mainly driven by virally transfected of Channelrhodopsin-2 (ChR2) gene, which also requires high irradiance and complex in vitro stimulation systems. Additionally, despite the extensive application of optogenetics in neuroscience, the question of what transcriptome changes does optogenetic stimulation induced in developing NSCs have not been elucidated yet. To address these questions, we established a NSC line, expressing high light-sensitivity step-function opsin (SFO) variant of the chimeric channelrhodopsin, ChRFR(C167A) (~40x higher than ChR2), via the non-viral piggyBac transposon system. We set up a simple low-irradiance optogenetics stimulation-incubation system, which sufficiently induced depolarization in differentiating NSCs. We significantly enhance neurogenesis with low power optogenetic stimulation by 3 folds. Through microarray analysis, we have identified the genes and signaling pathways in axonal remodeling, synaptic plasticity and microenvironment modulation from optogenetic stimulation. Our results elucidate the transcriptome effects of optogenetics and the ability to drive neurogenesis with low irradiance optogenetics.

2017-11-04 | GSE106515 | GEO

A GENETIC, GENOMIC, AND COMPUTATIONAL RESOURCE FOR EXPLORING NEURAL CIRCUIT FUNCTION

Project description:The anatomy of many neural circuits is being characterized with increasing resolution, but their molecular properties remain mostly unknown. Here, we characterize gene expression patterns in distinct neural cell types of the Drosophila visual system using genetic lines to access individual cell types, the TAPIN-seq method to measure their transcriptomes, and a probabilistic method to interpret these measurements. We used these tools to build a resource of high-resolution transcriptomes for 100 driver lines covering 67 cell types. Combining these transcriptomes with recently reported connectomes helps characterize how information is transmitted and processed across a range of scales, from individual synapses to circuit pathways. We describe examples that include identifying neurotransmitters, including cases of co-release, generating functional hypotheses based on receptor expression, as well as identifying strong commonalities between different cell types.

2018-08-05 | GSE116969 | GEO

Differential quantitative proteome analysis of cerebellar flocculus on oculomotor behavior training mouse model

Project description:Oculomotor behavior model system is commonly employed to study the neural circuits and the cellular mechanisms underlying neural integration related to motor behavior. The flocculus is a small lobe at the posterior border of the middle cerebellar and involved in motor control to aid in the oculomotor system in the brain. However, only several studies have investigated the molecular mechanism of learning and memory in flocculus region using another approach than proteomics.

2020-03-20 | PXD008433 | Pride

Electrical and synaptic integration of glioma into neural circuits

Project description:Electrical and synaptic integration of glioma into neural circuits

| PRJNA554601 | ENA

Identification of cranial-specific neural crest genes by comparative transcriptomics

Project description:We employ RNA-seq of FACS sorted cell populations to identify genes that are enriched in cranial neural crest in relationship to the trunk. Transcriptional profiling of delaminating cranial and trunk neural crest subpopulations.

2016-06-24 | E-GEOD-75125 | biostudies-arrayexpress

Advanced Complexity and Short-Term Plasticity of Neural Activity in Reciprocally Connected Human Cerebral Organoids

Project description:An inter-regional cortical tract is one of the most fundamental architectural motifs that integrates neural circuits to orchestrate and generate complex functions of the human brain. To understand the mechanistic significance of inter-regional projections on development of neural circuits, we investigated an in vitro neural tissue model for inter-regional connections, in which two cerebral organoids are connected with a bundle of reciprocally extended axons. The connected organoids produced more complex and intense oscillatory activity than conventional or directly fused cerebral organoids, suggesting the inter-organoid axonal connections enhance and support the complex network activity. In addition, optogenetic stimulation of the inter-organoid axon bundles could entrain the activity of the organoids and induce robust plasticity of the macroscopic circuit. These results demonstrated that the projection axons could serve as a structural hub that boosts functionality of the organoid-circuits. This model could contribute to further investigation on development and functions of macroscopic neuronal circuits in vitro.

2024-02-22 | GSE190729 | GEO

Age-associated bidirectional modulation of gene expression in single identified R15 neuron of Aplysia

Project description:Despite the advances in our understanding of aging-associated behavioral decline, we know relatively little about how aging affect neural circuits that underlie specific behaviors. Specifically, we know little about how aging affect expression of genes in specific neural circuits. We have now addressed this problem by exploring a cholinergic neuron R15, an identified neuron of marine snail Aplysia. R15 is characterized by bursting action potentials and is implicated in reproduction, osmoregulation and locomotion.

2014-02-05 | GSE46618 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data