A Transcriptomic Atlas of Mouse Cerebellar Cortex Reveals Novel Cell Types (Pre)
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PROVIDER: PRJNA726300 | ENA |
REPOSITORIES: ENA
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Project description:A Transcriptomic Atlas of Mouse Cerebellar Cortex Reveals Novel Cell Types (Pre)
| PRJNA726301 | ENA
Project description:The cerebellar cortex is a well-studied brain structure with diverse roles in motor learning, coordination, cognition, and autonomic regulation. Nonetheless, a complete inventory of cerebellar cell types is presently lacking. We used high-throughput transcriptional profiling to profile more than 600,000 nuclei and molecularly define cell types across individual lobules of the adult mouse cerebellum. Purkinje neurons showed considerable regional specialization, with the greatest diversity occurring in the posterior lobules. For multiple types of cerebellar interneurons, the molecular variation within each type was more continuous, rather than discrete. For the unipolar brush cells (UBCs)—an interneuron population previously subdivided into discrete populations—the continuous variation in gene expression was associated with a graded continuum of electrophysiological properties. Most surprisingly, we found that molecular layer interneurons (MLIs) were composed of two molecularly and functionally distinct types. Both show a continuum of morphological variation through the thickness of the molecular layer, but electrophysiological recordings revealed marked differences between the two types in spontaneous firing, excitability, and electrical coupling. Together, these findings provide the first comprehensive cellular atlas of the cerebellar cortex, and outline a methodological and conceptual framework for the integration of molecular, morphological, and physiological ontologies for defining brain cell types.
2021-01-22 | GSE165371 | GEO
Project description:A transcriptomic atlas of mouse cerebellar cortex reveals novel cell types
| PRJNA694175 | ENA
Project description:The cerebellar cortex is a well-studied brain structure with diverse roles in motor learning, coordination, cognition and autonomic regulation. However, a complete inventory of cerebellar cell types is currently lacking. Here, using recent advances in high-throughput transcriptional profiling1-3, we molecularly define cell types across individual lobules of the adult mouse cerebellum. Purkinje neurons showed considerable regional specialization, with the greatest diversity occurring in the posterior lobules. For several types of cerebellar interneuron, the molecular variation within each type was more continuous, rather than discrete. In particular, for the unipolar brush cells-an interneuron population previously subdivided into discrete populations-the continuous variation in gene expression was associated with a graded continuum of electrophysiological properties. Notably, we found that molecular layer interneurons were composed of two molecularly and functionally distinct types. Both types show a continuum of morphological variation through the thickness of the molecular layer, but electrophysiological recordings revealed marked differences between the two types in spontaneous firing, excitability and electrical coupling. Together, these findings provide a comprehensive cellular atlas of the cerebellar cortex, and outline a methodological and conceptual framework for the integration of molecular, morphological and physiological ontologies for defining brain cell types.
| S-EPMC8494635 | biostudies-literature
Project description:Cerebellar cortex expression in ataxia-telangiectasia patients and normal controls. The neurodegenerative disease known as ataxia-telangiectasia (A-T) is caused by the absence of the ATM (A-T mutated) protein. A long-standing mystery surrounding A-T is why cerebellar Purkinje cells (PCs) appear uniquely vulnerable to ATM-deficiency. Here, we present that 5-hydroxymethylcytosine (5hmC), a newly recognized epigenetic marker found at high levels in neurons, is substantially reduced in human A-T and Atm-/- mouse cerebellar PCs. TET1, an enzyme that converts 5mC to 5hmC, responds to DNA damage. Manipulation of TET1 activity directly affects neuronal cell cycle reentry and cell death after the induction of DNA damage. Quantitative, genome-wide analysis of 5hmC of samples from human cerebellum showed that in ATM-deficiency there is a remarkable genome-wide reduction of 5hmC enrichment at both proximal and distal regulatory elements. These results reveal a role of TET1-mediated 5hmC in DNA damage response, and provide insights into the basis of a PC-specific DNA demethylation alteration in ATM-deficiency. Human frozen tissue was obtained from the NICHD Brain and Tissue Bank of Developmental Disorders at the University of Maryland, Baltimore, MD. RNA was prepared and run on an Illumina Human HT-12 v4 microarray. 3 ataxia-telangiectasia (A-T) cases and 4 normal controls.
2015-10-30 | E-GEOD-61019 | biostudies-arrayexpress
Project description:Cerebellar cortex expression in ataxia-telangiectasia patients and normal controls. The neurodegenerative disease known as ataxia-telangiectasia (A-T) is caused by the absence of the ATM (A-T mutated) protein. A long-standing mystery surrounding A-T is why cerebellar Purkinje cells (PCs) appear uniquely vulnerable to ATM-deficiency. Here, we present that 5-hydroxymethylcytosine (5hmC), a newly recognized epigenetic marker found at high levels in neurons, is substantially reduced in human A-T and Atm-/- mouse cerebellar PCs. TET1, an enzyme that converts 5mC to 5hmC, responds to DNA damage. Manipulation of TET1 activity directly affects neuronal cell cycle reentry and cell death after the induction of DNA damage. Quantitative, genome-wide analysis of 5hmC of samples from human cerebellum showed that in ATM-deficiency there is a remarkable genome-wide reduction of 5hmC enrichment at both proximal and distal regulatory elements. These results reveal a role of TET1-mediated 5hmC in DNA damage response, and provide insights into the basis of a PC-specific DNA demethylation alteration in ATM-deficiency.
2015-10-30 | GSE61019 | GEO
Project description: Not available
| S-EPMC8828463 | biostudies-literature
Project description:We investigated molecular changes during human, chimpanzee, and rhesus macaque postnatal brain development at the transcriptome, proteome, and metabolome levels in two brain regions: the prefrontal cortex (PFC) that is involved in several human-specific cognitive processes, and the cerebellar cortex (CBC) that may be functionally more conserved. We find a nearly three-fold excess of human-specific gene expression changes in PFC compared to CBC. The most prominent human-specific mRNA expression pattern in the PFC is a developmental delay of approximately 5 years in the expression of genes associated with learning and memory, such as synaptic transmission and long-term potentiation. This pattern is supported by correlated changes in concentrations of proteins and the respective neurotransmitters and its magnitude is beyond the shift expected from the life-histories of the species. Mechanistically, it might be driven by change in timing of expression of four or more transcription factors. We speculate that delayed synaptic maturation in PFC may play a role in the emergence of human-specific cognitive abilities. Keywords: Age series Human, chimpanzee and rhesus macaque post-mortem brain samples from the cerebellar cortex were collected. The age ranges of the individuals in all three species covered the respective species' postnatal maturation period from infancy to old adulthood. RNA extracted from the dissected tissue was hybridized to Affymetrix® Human Gene 1.0 ST arrays. CBC samples.
2011-12-09 | E-GEOD-22569 | biostudies-arrayexpress
Project description:Human cerebellar development is precisely orchestrated by molecular regulatory networks. Here, we combined single-cell transcriptomics, spatial transcriptomics and chromatin accessibility states to systematically depict an integrative temporal-spatial landscape of human fetal cerebellar development. The multiomic data reveal molecular networks, providing an informative regulatory map to show how and when cell fates are determined. Spatial transcriptomics illustrated the distinct molecular signatures of the progenitors, Purkinje cells and granule cells located in different regions of the developing cerebellar cortex. We identified RORB as a new marker of developing human Purkinje cells, which was not expressed in mice. In addition, the RL progenitors highly expressed the human-specific gene ARHGAP11B , and ARHGAP11B expression led to cerebellar cortex expansion and folding in mice. We finally mapped the genes and single-nucleotide polymorphisms (SNPs) of diseases related to cerebellar dysfunction onto cell types, indicating the cellular basis and possible pathogenesis mechanisms of neuropsychiatric disorders.
2023-11-01 | GSE165657 | GEO
Project description:Gene expression in primate postnatal brain through lifespan - cerebellar cortex
| PRJNA129099 | ENA