Human Pluripotent Stem Cell-derived Medium Spiny Neurons (hMSNs) Exhibit Acute and Chronic Responses to Dopamine
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA800804 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17771600_1.fastq.gz | Fastqsanger.gz | |||
| SRR17771600_2.fastq.gz | Fastqsanger.gz | |||
| SRR17771601_1.fastq.gz | Fastqsanger.gz | |||
| SRR17771601_2.fastq.gz | Fastqsanger.gz | |||
| SRR17771602_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Here, we performed RNA-seq of hMSNs in triplicate (20-30 million reads per sample) exposed to dopamine, assessed their responses over time, and also compared their transcriptomic and functional responses to acute and chronic exposures. We also identified responses to agonists of interest. From this work, we identified ranges of experimental conditions that elicited cellular responses, identified specific genes and ontological functions induced by dopamine exposure, and observed desensitization to chronic exposures. These results provide a foundation on which to further develop hMSN models and to derive context for and comparisons between human and rodent responses.
2022-04-20 | GSE195492 | GEO
Project description:Yapo2017- cAMP/PKA signalling in D1 dopamine receptor expressing medium-spiny neurons
This model is described in the article:
Detection of phasic dopamine
by D1 and D2 striatal medium spiny neurons.
Yapo C, Nair AG, Clement L, Castro
LR, Hellgren Kotaleski J, Vincent P.
J. Physiol. (Lond.) 2017 Aug; :
Abstract:
The phasic release of dopamine in the striatum determines
various aspects of reward and action selection, but the
dynamics of dopamine effect on intracellular signalling remains
poorly understood. We used genetically-encoded FRET biosensors
in striatal brain slices to quantify the effect of transient
dopamine on cAMP or PKA-dependent phosphorylation level, and
computational modelling to further explore the dynamics of this
signalling pathway. Medium-sized spiny neurons (MSNs), which
express either D1 or D2 dopamine receptors, responded to
dopamine by an increase or a decrease in cAMP, respectively.
Transient dopamine showed similar sub-micromolar efficacies on
cAMP in both D1 and D2 MSNs, thus challenging the commonly
accepted notion that dopamine efficacy is much higher on D2
than on D1 receptors. However, in D2 MSNs, the large decrease
in cAMP level triggered by transient dopamine did not translate
in a decrease in PKA-dependent phosphorylation level, owing to
the efficient inhibition of Protein Phosphatase 1 by DARPP-32.
Simulations further suggested that D2 MSNs can also operate in
a "tone-sensing" mode, allowing them to detect transient dips
in basal dopamine. Overall, our results show that D2 MSNs may
sense much more complex patterns of dopamine than previously
thought. This article is protected by copyright. All rights
reserved.
This model is hosted on
BioModels Database
and identified by:
MODEL1701170000.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2017-08-16 | MODEL1701170000 | BioModels
Project description:Yapo2017 - A2AR/cAMP/PKA signalling in D2 dopamine receptor expressing medium-spiny neurons
This model is described in the article:
Detection of phasic dopamine
by D1 and D2 striatal medium spiny neurons.
Yapo C, Nair AG, Clement L, Castro
LR, Hellgren Kotaleski J, Vincent P.
J. Physiol. (Lond.) 2017 Aug; :
Abstract:
The phasic release of dopamine in the striatum determines
various aspects of reward and action selection, but the
dynamics of dopamine effect on intracellular signalling remains
poorly understood. We used genetically-encoded FRET biosensors
in striatal brain slices to quantify the effect of transient
dopamine on cAMP or PKA-dependent phosphorylation level, and
computational modelling to further explore the dynamics of this
signalling pathway. Medium-sized spiny neurons (MSNs), which
express either D1 or D2 dopamine receptors, responded to
dopamine by an increase or a decrease in cAMP, respectively.
Transient dopamine showed similar sub-micromolar efficacies on
cAMP in both D1 and D2 MSNs, thus challenging the commonly
accepted notion that dopamine efficacy is much higher on D2
than on D1 receptors. However, in D2 MSNs, the large decrease
in cAMP level triggered by transient dopamine did not translate
in a decrease in PKA-dependent phosphorylation level, owing to
the efficient inhibition of Protein Phosphatase 1 by DARPP-32.
Simulations further suggested that D2 MSNs can also operate in
a "tone-sensing" mode, allowing them to detect transient dips
in basal dopamine. Overall, our results show that D2 MSNs may
sense much more complex patterns of dopamine than previously
thought. This article is protected by copyright. All rights
reserved.
This model is hosted on
BioModels Database
and identified by:
MODEL1701170001.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2017-08-16 | MODEL1701170001 | BioModels
Project description:Mice lacking the TrkB receptor and expressing a ribosomal HA tag in dopamine D1 receptor-expressing neurons (D1-Cre-flTrkB-RT mice) were used. A subset of these mice (14.4%) display repetitive, stereotypic rotational behavior. Polyribosome immunoprecipitation from dorsal striatum D1-medium spiny neurons was used to isolate cell-type specific RNA. Translatomes of 4-week old mice with and without repetitive behavior, as well as control (D1-Cre-RT mice) were compared using RNA-sequencing.
2021-03-01 | GSE146274 | GEO
Project description:The striatum is the interface between dopamine reward signals and cortico-basal ganglia circuits that mediate diverse behavioral functions. Medium spiny neurons (MSNs) constitute the vast majority of striatal neurons and are traditionally classified as direct- or indirect-pathway neurons. However, that traditional model does not explain the anatomical and functional diversity of MSNs. Here, we defined molecularly distinct MSN types in the primate striatum, including (1) dorsal striatum MSN types associated with striosome and matrix compartments, (2) ventral striatum types associated with the nucleus accumbens shell and olfactory tubercle, and (3) an MSN-like type restricted to mu-opioid receptor rich islands in the ventral striatum. These results lay the foundation for achieving cell type-specific transgenesis in the primate striatum and provide a blueprint for investigating circuit-specific processing.
2021-11-01 | GSE167920 | GEO
Project description:mRNAseq for baseline transcriptional profiling of D1 and D2 receptor-expressing medium spiny neurons from 5-6 month Q175 mice compared to WT littermates.
2018-09-01 | GSE103345 | GEO
Project description:Recent advances in single-cell technologies are paving the way to a comprehensive understanding of the cellular complexity in the brain. Protocols for single-cell transcriptomics combine a variety of sophisticated methods in order to isolate heavily interconnected and heterogeneous neuronal cell types in a relatively intact and healthy state. The emphasis of single-cell transcriptome studies has thus far been on comparing library generation and sequencing techniques that enable measurement of the minute amounts of starting material from a single cell. However, in order for data to be comparable, standardized cell isolation techniques are essential. Here, we analyzed and simplified methods for the different steps critically involved in single-cell isolation from brain. These include highly region-specific cellular labelling compatible with use of stereotaxic coordinates, enzymatic digestion, tissue trituration, and improved methods for efficient fluorescence-activated cell sorting in samples containing high degree of debris from the neuropil. The methods are exemplified using medium spiny neurons (MSN) from dorsomedial striatum, a cell type that is clinically relevant for disorders of the basal ganglia, including psychiatric and neurodegenerative diseases. We present single-cell RNA sequencing (scRNA-Seq) data from D1 and D2 dopamine receptor expressing MSN subtypes. We illustrate the need for single-cell resolution by comparing to available population-based gene expression data of striatal medium spiny neuron subtypes. Our findings contribute towards standardizing important steps of single-cell isolation from adult brain tissue to increase comparability of data. Furthermore, our data newly define the transcriptome of medium spiny neurons at unprecedented resolution and identify novel subtype specific marker genes in this important cell type
2018-05-01 | GSE112177 | GEO
Project description:Gene desensitization in response to a repeated stimulus is a complex phenotype important across homeostatic and disease processes, including addiction, learning, and memory. These complex phenotypes are being characterized and connected to important physiologically relevant functions in rodent systems but are difficult to capture in human models where even acute responses to important neurotransmitters are understudied. Here through transcriptomic analysis, we map the dynamic responses of human stem cell-derived medium spiny neuron-like cells (hMSN-like cells) to dopamine. Furthermore, we show that these human neurons can reflect and capture cellular desensitization to chronic versus acute administration of dopamine. These human cells are further able to capture complex receptor crosstalk in response to the pharmacological perturbations of distinct dopamine receptor subtypes. This study demonstrates the potential utility and remaining challenges of using human stem cell-derived neurons to capture and study the complex dynamic mechanisms of the brain.
| S-EPMC9100557 | biostudies-literature
Project description:The goal of this experiment was to determine how dopamine receptor activation in medium spiny neurons alters rapid transcriptional programs. To identify genes altered by dopamine, we used a rat primary striatal neuronal culture system in which striatal neurons were removed from the rat brain at embryonic day 18, cultured for 11 days in vitro using standard neuronal conditions, and treated neurons with either vehicle (neurobasal media) or dopamine (at a concentration of 1µM) for 1hr. This dataset contains PolyA+ RNA-seq results from this experiment, in which we identified 100 upregulated genes and 3 downregulated genes after dopamine stimulation using DESeq2 pipelines.
2020-06-24 | GSE137568 | GEO
Project description:The cellular heterogeneity of the brain confounds efforts to elucidate the biological properties of distinct neuronal populations. Using Bacterial Artificial Chromosome (BAC) transgenic mice which express EGFP-tagged ribosomal protein L10a in defined cell populations, we have developed a methodology to affinity purify polysomal mRNAs from genetically defined cell populations in the brain. The utility of this approach is illustrated by the comparative analysis of four types of neurons, revealing hundreds of genes that distinguish these four cell populations. We find that even two morphologically indistinguishable, intermixed subclasses of medium spiny neuron display vastly different translational profiles and present examples of the physiological significance of such differences. This genetically targeted Translating Ribosome Affinity Purification (TRAP) methodology is a generalizable method useful for the identification of molecular changes in any genetically defined cell type in response to genetic alterations, disease, or pharmacological perturbations. Keywords: Cell Type Comparison
2008-11-14 | GSE13384 | GEO