Heterogeneity of Purkinje cells orchestrates cerebellar development
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE256438 | GEO | 2025/03/01
REPOSITORIES: GEO
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Project description:We performed gene-expression analysis of mouse Purkinje cells as a model M-bM-^@M-^\single-type neuronM-bM-^@M-^]. DNA microarray analysis detected at least 7,055 genes in Purkinje cells, most of which are classified into functional molecule categories. Our comparative analysis between Purkinje cells and the granule cell layer showed that the characteristic expression pattern in Purkinje cells was particularly represented by M-bM-^@M-^\the neural communication systemM-bM-^@M-^] components. Pukinje cells and granule cell layer of the mouse cerebellum were collected by laser microdissection for RNA extraction and hybridization on Affymetrix microarrays.
2013-01-17 | E-GEOD-26749 | biostudies-arrayexpress
Project description:We performed gene-expression analysis of mouse Purkinje cells as a model “single-type neuron”. DNA microarray analysis detected at least 7,055 genes in Purkinje cells, most of which are classified into functional molecule categories. Our comparative analysis between Purkinje cells and the granule cell layer showed that the characteristic expression pattern in Purkinje cells was particularly represented by “the neural communication system” components.
2013-01-17 | GSE26749 | GEO
Project description:Gene expression studies in cerebella isolated from 5 week old wildtype or transgenic mice (C57BL/6) overexpressing Ronin in Purkinje cells were generated. RNA was isolated from cerebella of 3 transgenic animals at 5 weeks of agee and 3 wildtype litter mates.
2021-06-10 | GSE176518 | GEO
Project description:Research on human cerebellar development and disease has been hampered by the need for a human cell-based system that recapitulates the human cerebellum's cellular diversity and functional features. Here, we report a human organoid model (hCerOs) capable of developing the complex cellular diversity of the fetal cerebellum, including human-specific rhombic lip progenitor populations that have never been generated in vitro prior to this study. Two months old hCerOs form distinct cytoarchitectural features, including laminar organized layering and create functional connections between inhibitory and excitatory neurons that display coordinated network activity. Long-term culture of hCerOs allows for healthy survival and maturation of Purkinje cells that display molecular and electrophysiological hallmarks of their in vivo counterparts, addressing a long-standing challenge in the field. This study therefore provides a physiologically relevant, all-human model system to elucidate the cell type specific mechanisms governing cerebellar development and disease.
2023-11-21 | GSE247974 | GEO
Project description:The signalling protein PKCγ is a major regulator of Purkinje cell development and synaptic function. We have shown previously that increased PKCγ activity impairs dendritic development of cerebellar Purkinje cells. Mutations in the protein kinase Cγ gene (PRKCG) cause spinocerebellar ataxia type 14 (SCA14). In a transgenic mouse model of SCA14 expressing the human S361G mutation, Purkinje cell dendritic development is impaired in cerebellar slice cultures similar to pharmacological activation of PKC. The mechanisms of PKCγ-driven inhibition of dendritic growth are still unclear. Using immunoprecipitation-coupled mass spectrometry analysis we have identified Collapsin Response Mediator Protein 2 (CRMP2) as a protein interacting with constitutive active PKCγ(S361G) and confirmed the interaction with the Duolink™ proximity ligation assay. We show that in cerebellar slice cultures from PKCγ(S361G)- mice, phosphorylation of CRMP2 at the known PKC target site Thr555 is increased in Purkinje cells confirming phosphorylation of CRMP2 by PKCγ. miRNA-mediated CRMP2 knockdown decreased Purkinje cell dendritic outgrowth in dissociated cerebellar cultures as did the transfection of CRMP2 mutants with a modified Thr555 site. In contrast, dendritic development was normal after wildtype CRMP2 overexpression. In a novel knock-in mouse expressing only the phospho-defective T555A-mutant CRMP2, Purkinje cell dendritic development was reduced in dissociated cultures. This reduction could be rescued by transfecting wildtype CRMP2 but only partially by the phospho-mimetic T555D-mutant. Our findings establish CRMP2 as an important target of PKCγ phosphorylation in Purkinje cells mediating its control of dendritic development. Dynamic regulation of CRMP2 phosphorylation via PKCγ is required for its correct function.
2022-02-24 | PXD020124 | Pride
Project description:Previous studies in bulk tissue suggest that there are abundant expression quantitative trait loci (eQTLs) in human brain. This sample series is of cerebellar Purkinje cells isolated using laser capture microdissection from human cases without neurological disease but of known genotypes. These data may be helpful in confirming eQTLs in bulk tissue or in mapping other gene expression traits in an enriched neuronal population. Authorized Access data: Mapping of GEO sample accessions to dbGaP subject/sample IDs is available through dbGaP Authorized Access, see http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000249 The aim of this study was to examine gene expression in isolated purkinje cells from the human cerebellum. We obtained frozen brain tissue from the cerebellum. We stained sections with cresyl violet and separated Purkinje cells based on morphology and location within the cerebellum using laser capture microdissection. Expression analyses were then performed.
2013-01-01 | E-GEOD-37205 | biostudies-arrayexpress
Project description:Human Cerebellar Organoids with functional Purkinje Cells
| PRJNA1041338 | ENA
Project description:Spinocerebellar Ataxias (SCAs) are a group of genetic diseases characterized by progressive ataxia and neurodegeneration, often in cerebellar Purkinje neurons. A SCA1 mouse model, Pcp2-ATXN1[30Q]D776, has severe ataxia in absence of progressive Purkinje neuron degeneration and death. Previous RNA-seq analyses identified cerebellar up-regulation of the peptide hormone Cholecystokinin (Cck) in Pcp2-ATXN1[30Q]D776 mice. Importantly, absence of Cck1 receptor (Cck1R) in Pcp2-ATXN1[30Q]D776 mice confers a progressive disease with Purkinje neuron death. A Cck1R agonist, A71623 administered to Pcp2-ATXN1[30Q]D776;Cck-/- and Pcp2-AXTN1[82Q] mice dampened Purkinje neuron pathology and associated deficits in motor performance. In addition, A71623 administration improved motor performance of Pcp2-ATXN2[127Q] SCA2 mice. Moreover, the Cck1R agonist A71623 corrected mTORC1 signaling and improved expression of calbindin in cerebella of AXTN1[82Q] and ATXN2[127Q] mice. These results indicate that manipulation of the Cck-Cck1R pathway is a potential therapeutic target for treatment of diseases involving Purkinje neuron degeneration.
2022-01-11 | GSE180969 | GEO
Project description:Mitochondria vary in morphology and function in different tissues, however little is known about their molecular diversity among cell types. To investigate mitochondrial diversity in vivo, we developed an efficient protocol to isolate cell type-specific mitochondria based on a new MitoTag mouse. We profiled the mitochondrial proteome of three major neural cell types in cerebellum and identified a substantial number of differential mitochondrial markers for these cell types in mice and humans. Based on predictions from these proteomes, we demonstrate that astrocytic mitochondria metabolize long-chain fatty acids more efficiently than neurons. Moreover, we identified Rmdn3 as a major determinant of ER-mitochondria proximity in Purkinje cells. Our novel approach enables exploring mitochondrial diversity on the functional and molecular level in many in vivo contexts.
2019-09-03 | PXD010772 | Pride
Project description:Despite the canonical homogeneous character of its organization, the cerebellum plays differential computational roles in distinct sensorimotor behaviors. Previously, we showed that Purkinje cell (PC) activity differs between zebrin-negative (Z-) and zebrin-positive (Z+) modules (Zhou et al., 2014). Here, using gain-of-function and loss-of-function mouse models, we show that transient receptor potential cation channel C3 (TRPC3) controls the simple spike activity of Z-, but not Z+ PCs. In addition, TRPC3 regulates complex spike rate and their interaction with simple spikes, exclusively in Z- PCs. At the behavioral level, TRPC3 loss-of-function mice show impaired eyeblink conditioning, which is related to Z- modules, whereas compensatory eye movement adaptation, linked to Z+ modules, is intact. Together, our results indicate that TRPC3 is a major contributor to the cellular heterogeneity that introduces distinct physiological properties in PCs, conjuring functional heterogeneity in cerebellar sensorimotor integration.
| S-EPMC6733575 | biostudies-literature