Foxp striatal compensation (RNA-Seq)
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE228825 | GEO | 2024/04/04
REPOSITORIES: GEO
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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: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: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:The mammalian striatum is involved in many complex behaviors and yet is largely composed of a single neuron class: the spiny projection neuron (SPN). It is unclear to what extent the functional specialization of the striatum is due to the molecular specialization of SPN subtypes. We sought to define the molecular and anatomical diversity of adult SPNs using single-cell RNA-seq and quantitative RNA in situ hybridization (ISH). We computationally distinguished discrete versus continuous heterogeneity in scRNA-seq data and found that SPNs in the striatum can be classified into four major discrete types with no implied spatial relationship between them. Within these discrete types, we find continuous heterogeneity encoding spatial gradients of gene expression and defining anatomical location in a combinatorial mechanism. Our results suggest that neuronal circuitry has a substructure at far higher resolution than is typically interrogated which is defined by the precise identity and location of a neuron.
2019-11-17 | GSE139412 | GEO
Project description:Solid pseudopapillary neoplasm (SPN) of pancreas is a rare pancreatic neoplasm with a low metastatic potential. Up to 10% of patients with localized disease at presentation will develop systemic metastases, usually in the peritoneum or the liver. Due to the rarity of SPNs and the overall excellent prognosis, reliable prognostic factors to predict malignant biological behavior remain undetermined. Therefore, we aimed to define clinical, histological, and microRNA patterns that are associated with metastatic disease. We conducted a retrospective single center study on all patients operated for SPN of pancreas between 1995 and 2018. Clinical and pathological data were collected, and expression patterns of 2578 human microRNAs were analyzed using microRNA array (Affimetrix 4.1) in normal pancreases (NPs), localized tumors (LTs), and metastatic tumors (MTs). The diagnosis of SPN was confirmed in 35 patients who included 28 females and 3 males, with a mean age of 33.8 ± 13.9 years. The only clinical factor associated with metastases was tumor size (mean tumor size 5.20 ± 3.78 in LT versus 8.13± 1.03 in MT, p < 0.012). Microscopic features of malignancy were not associated with metastases, nor were immunohistochemical stains, including the proliferative index KI67. Higher expressions of miR-184, miR-10a, and miR-887, and lower expressions of miR-375, miR-217, and miR-200c were observed in metastatic tissues on microarray, and validated by real-time polymerase chain reaction. Hierarchal clustering demonstrated that the microRNA expression pattern of MTs was significantly different from that of LTs. The only clinical factor associated with metastases of SPN of pancreas was tumor size. Histological features and immunohistological staining were not predictive of metastases. A panel of six microRNAs was differentially expressed in MTs, and these findings could potentially be used to predict tumor behavior. Validation of these results is needed in larger series.
2020-02-24 | GSE140719 | 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