Continuous and discrete neuron types of the adult murine striatum
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE139412 | GEO | 2019/11/17
REPOSITORIES: GEO
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Project description:The striatum is organized into two major outputs formed by striatal projection neuron (SPN) subtypes with distinct molecular identities. In addition, the histochemical division into patch and matrix compartments represents an additional spatial organization, proposed to mirror a functional specialization in a motor-motivation dimension. To map the molecular diversity of SPNs in the context of the patch and matrix division, we genetically labeled mu-opioid receptor (Oprm1) expressing striatal neurons and performed single-nucleus RNA sequencing (snRNA-seq). This allowed us to establish new molecular definitions of the patch-matrix compartments, resulting in a molecular code for mapping patch SPNs at the cellular level. In addition, Oprm1 expression labeled exopatch SPNs, which we found to be molecularly distinct from both patch as well as neighboring matrix SPNs, thereby forming a separate molecular entity. At the cell-type level, we found an unexpected SPN diversity, leading to the identification of a new Col11a1+ striatonigral SPN type. At the tissue level, we found that mapping the spatial expression of a number of markers revealed new definitions of spatial domains in the striatum, which were conserved in the non-human primate brain. Interestingly, the spatial markers were cell-type independent and instead represented a spatial code that was found across all SPNs within a spatially restricted domain. This spatiomolecular map establishes a formal system for targeting and studying the striatal subregions and SPNs subtypes, beyond the classical striatonigral and striatopallidal division.
2019-11-01 | GSE139265 | GEO
Project description:Solid-pseudopapillary neoplasm of pancreas(SPN), ductal adenocarcinoma(PCA), neuroendocrine tumor(NET) and non-neoplastic pancreas. To investigate the specific gene expression of SPN compared to other types of pancreatic tumor, we analyzed large-scale gene expressioin analysis to identify the molecular signature that may affect SPN tumorigenesis. Differentially expressed genes were analyzed on SPNs, PCAs, NETs and Non-neoplastic tissues. Solid-pseudopapillary neoplasm (SPN) is an uncommon pancreatic tumor with distinct clinicopathologic features. SPNs are characterized by mutations in exon 3 of CTNNB1. However, little is known about the gene and microRNA expression profiles of SPNs. Thus, we sought to characterize SPN-specific gene expression and identify the signaling pathways activated in these tumors. The mRNA expression profile of 14 SPNs, 6 pancreatic adenocarcinomas (PCAs), 6 pancreatic neuroendocrine tumors (NETs), and five non-neoplastic pancreatic tissues were analyzed.
2013-12-31 | E-GEOD-43795 | biostudies-arrayexpress
Project description:Continuous and discrete neuron types of the adult murine striatum
| PRJNA589979 | ENA
Project description:Spiny projection neurons (SPNs) of the striatum are critical in integrating neurochemical information to coordinate motor and reward-based behavior. Mutations in the regulatory transcription factors expressed in SPNs can result in neurodevelopmental disorders (NDDs). Paralogous transcription factorsFoxp1andFoxp2, which are both expressed in the dopamine receptor 1 (D1) expressing SPNs, are known to have variants implicated in NDDs. Utilizing mice with a D1-SPN specific loss ofFoxp1,Foxp2, or both and a combination of behavior, electrophysiology, and single-nuclei RNA (snRNA-seq) and single-nuclei Assay for Transposase-Accessible Chromatin sequencing (snATAC-seq), we find that loss of both genes results in impaired motor and social behavior as well as increased firing of the D1-SPNs. Differential gene expression analysis of snRNA-seq data implicates genes involved in autism risk, altered electrophysiological properties, and neuronal development and function. These data indicate complementary roles betweenFoxp1andFoxp2in the D1-SPNs.
2024-04-04 | GSE228825 | GEO
Project description:Spiny projection neurons (SPNs) of the striatum are critical in integrating neurochemical information to coordinate motor and reward-based behavior. Mutations in the regulatory transcription factors expressed in SPNs can result in neurodevelopmental disorders (NDDs). Paralogous transcription factorsFoxp1andFoxp2, which are both expressed in the dopamine receptor 1 (D1) expressing SPNs, are known to have variants implicated in NDDs. Utilizing mice with a D1-SPN specific loss ofFoxp1,Foxp2, or both and a combination of behavior, electrophysiology, and single-nuclei RNA (snRNA-seq) and single-nuclei Assay for Transposase-Accessible Chromatin sequencing (snATAC-seq), we find that loss of both genes results in impaired motor and social behavior as well as increased firing of the D1-SPNs. Differential gene expression analysis of snRNA-seq data implicates genes involved in autism risk, altered electrophysiological properties, and neuronal development and function. These data indicate complementary roles betweenFoxp1andFoxp2in the D1-SPNs.
2024-04-04 | GSE228823 | GEO
Project description:Solid-pseudopapillary neoplasm of pancreas (SPN), ductal adenocarcinoma (PCA), neuroendocrine tumor (NET) and non-neoplastic pancreas. comparison with gene expression of tumors and non-tumors To investigate the specific microRNA expression of SPN compared to other types of pancreatic tumor, we analyzed large-scale microRNA expressioin analysis to identify the molecular signature that may affect SPN tumorigenesis with mRNA expression profiles. Differentially expressed microRNAs were analyzed on SPNs, PCAs, NETs and Non-neoplastic tissues.
2013-12-31 | E-GEOD-43796 | biostudies-arrayexpress
Project description:Solid-pseudopapillary neoplasm of pancreas(SPN), ductal adenocarcinoma(PCA), neuroendocrine tumor(NET) and non-neoplastic pancreas. To investigate the specific gene expression of SPN compared to other types of pancreatic tumor, we analyzed large-scale gene expressioin analysis to identify the molecular signature that may affect SPN tumorigenesis. Differentially expressed genes were analyzed on SPNs, PCAs, NETs and Non-neoplastic tissues.
2013-12-31 | GSE43795 | GEO
Project description:The brain executes control of nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from numerous supraspinal regions to the spinal cord. Despite their physiological and clinical relevance, a comprehensive molecular characterization of SPNs is still lacking. Here, we use retrograde labeling, whole-brain imaging, and high-throughput transcriptional profiling to generate a unified brain-wide anatomic and transcriptomic atlas of adult mouse SPNs at single-cell resolution. We transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain generated by the Allen Institute for Brain Science within the BRAIN Initiative Cell Census Network (BICCN). This SPN taxonomy reveals a three-component organization of SPNs: (1) molecularly homogeneous excitatory SPNs from the cortex, red nucleus, and cerebellum with somatotopic spinal terminations suitable for point-to-point communication; (2) highly heterogeneous excitatory and inhibitory populations in the reticular formation with broad spinal termination patterns, thus suitable for relaying commands related to the activities of the entire spinal cord; and (3) modulatory neurons expressing slow-acting neurotransmitters and/or neuropeptides in the hypothalamus, midbrain, and reticular formation for gain control of brain-spinal signals. Within each of these components, this atlas revealed additional insights. From components (2) and (3), we discovered a LIM homeobox transcription factor code that parcellates the most transcriptionally complex population, reticulospinal neurons, into five molecularly distinct and spatially segregated populations. For neurons in component (1), we found transcriptional signatures of a subset of SPNs with large soma size and correlated these with fast-firing electrophysiological properties; thus, at least two different cable lines (namely, Pvalb/Kcng4/Spp1 positive and negative) with different electrophysiological properties might underlie the transmission of brain signals to the spinal cord. Together, by integrating the anatomy, molecular identity, and physiological properties, this study establishes a comprehensive taxonomy of brain-wide SPNs and provides insight into the functional organization of SPNs in mediating brain control of bodily functions.
2023-12-14 | GSE247597 | GEO
Project description:The brain executes control of nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from numerous supraspinal regions to the spinal cord. Despite their physiological and clinical relevance, a comprehensive molecular characterization of SPNs is still lacking. Here, we use retrograde labeling, whole-brain imaging, and high-throughput transcriptional profiling to generate a unified brain-wide anatomic and transcriptomic atlas of adult mouse SPNs at single-cell resolution. We transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain generated by the Allen Institute for Brain Science within the BRAIN Initiative Cell Census Network (BICCN). This SPN taxonomy reveals a three-component organization of SPNs: (1) molecularly homogeneous excitatory SPNs from the cortex, red nucleus, and cerebellum with somatotopic spinal terminations suitable for point-to-point communication; (2) highly heterogeneous excitatory and inhibitory populations in the reticular formation with broad spinal termination patterns, thus suitable for relaying commands related to the activities of the entire spinal cord; and (3) modulatory neurons expressing slow-acting neurotransmitters and/or neuropeptides in the hypothalamus, midbrain, and reticular formation for gain control of brain-spinal signals. Within each of these components, this atlas revealed additional insights. From components (2) and (3), we discovered a LIM homeobox transcription factor code that parcellates the most transcriptionally complex population, reticulospinal neurons, into five molecularly distinct and spatially segregated populations. For neurons in component (1), we found transcriptional signatures of a subset of SPNs with large soma size and correlated these with fast-firing electrophysiological properties; thus, at least two different cable lines (namely, Pvalb/Kcng4/Spp1 positive and negative) with different electrophysiological properties might underlie the transmission of brain signals to the spinal cord. Together, by integrating the anatomy, molecular identity, and physiological properties, this study establishes a comprehensive taxonomy of brain-wide SPNs and provides insight into the functional organization of SPNs in mediating brain control of bodily functions.
2023-12-14 | GSE247594 | 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