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Childhood cerebellar tumors mirror conserved fetal transcriptional programs

ABSTRACT: We used single-cell transcriptomics to study >60,000 cells from the developing murine cerebellum, and show that different molecular subgroups of childhood cerebellar tumors mirror the transcription of cells from distinct, temporally restricted cerebellar lineages.

PROVIDER: EGAS00001003170 | EGA |

REPOSITORIES: EGA

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Childhood Cerebellar Tumors Mirror Conserved Fetal Transcriptional Programs

Project description:The study of the origin and development of cerebellar tumours has been hampered by the complexity and heterogeneity of cerebellar cells that change over the course of development. We used single-cell transcriptomics to study >60,000 cells from the developing murine cerebellum, and show that different molecular subgroups of childhood cerebellar tumours mirror the transcription of cells from distinct, temporally restricted cerebellar lineages. Sonic Hedgehog medulloblastoma transcriptionally mirrors the granule cell hierarchy as expected, whereas Grp3-MB resemble Nestin+ve stem cells, Group 4 medulloblastomas resemble unipolar brush cells, and PFA/PFB ependymoma and cerebellar pilocytic astrocytoma resemble the pre-natal gliogenic progenitor cells. Furthermore, single-cell transcriptomics of human childhood cerebellar tumours demonstrates that many bulk tumours contain a mixed population of cells with divergent differentiation. Our data highlight cerebellar tumours as a disorder of early brain development, and provide a proximate explanation for the peak incidence of cerebellar tumours in early childhood.

2019-05-01 | GSE118068 | GEO

Childhood cerebellar tumours mirror conserved fetal transcriptional programs.

Project description: Not available

| S-EPMC6675628 | biostudies-literature

Childhood Cerebellar Tumors Mirror Conserved Fetal Transcriptional Programs

Project description:Childhood Cerebellar Tumors Mirror Conserved Fetal Transcriptional Programs

| PRJNA484319 | ENA

32ec0dbb-03e4-429e-b406-c610c3ca60f9 - samples

Project description:We used single-cell transcriptomics to study >60,000 cells from the developing murine cerebellum, and show that different molecular subgroups of childhood cerebellar tumors mirror the transcription of cells from distinct, temporally restricted cerebellar lineages.

| EGAD00001004318 | EGA

Temporal analysis of enhancers during mouse brain development reveals dynamic regulatory function and identifies novel regulators of cerebellar development.

Project description:In this study, we identified active enhancers in the mouse cerebellum at embryonic and postnatal stages establishing the first catalog of enhancers active during embryonic cerebellum development. The majority of cerebellar enhancers have dynamic activity between embryonic and postnatal development. Cerebellar enhancers were enriched for neural transcription factor binding sites with temporally specific expression. Putative gene targets displayed spatially restricted expression patterns, indicating cell-type specific expression regulation. Functional analysis of target genes indicated that enhancers regulate processes spanning several developmental epochs such as specification, differentiation and maturation. We use these analyses to discover one novel regulator and one novel marker of cerebellar development: Bhlhe22 and Pax3, respectively. We identified an enrichment of de novo mutations and variants associated with autism spectrum disorder in cerebellar enhancers. Our study provides insight into the dynamics of gene expression regulation by enhancers in the developing brain and delivers a rich resource of novel gene-enhancer associations providing a basis for future in-depth studies in the cerebellum.

2021-09-15 | GSE183697 | GEO

Generation of advanced cerebellar organoids for neurogenesis and neuronal network development

Project description:Neurons within the cerebellum form temporal-spatial connections through the cerebellum, and the entire brain. Organoid models provide an opportunity to model the early differentiation of the developing human cerebellum, which is difficult to study in vivo, and affords the opportunity to study neurodegenerative and neurodevelopmental diseases of the cerebellum. Previous cerebellar organoid models focused on early neuron generation and single cell activity. Here, we modify previous protocols to generate more mature cerebellar organoids that allow for the establishment of several classes of mature neurons during cerebellar differentiation and development, including the establishment of neural networks during whole organoid maturation. This will provide a means to study the generation of several more mature cerebellar cell types, including Purkinje cells, granule cells, interneurons expression as well as neuronal communication for biomedical, clinical, and pharmaceutical application.

2023-07-20 | GSE237855 | GEO

Cerebellar development

Project description:The Affymetrix GeneChip Mu11K was used to analyze the gene expression profile in developing mouse cerebellum (two GeneChips per E18, P7, P14, P21, and P56) to assist in the understanding of the genetic basis of cerebellar development in mice. The analysis showed 81.6% (10,321/12,654) of the genes represented on the GeneChip were expressed in the postnatal cerebellum, and among those, 8.7% (897/10,321) were differentially expressed with more than a two-fold change in their maximum and minimum expression levels during the developmental time course. The expression data (mean signal in relative unit) of all of these 897 differentially expressed genes were listed in GSM50(for E18), GSM51(for P7), GSM52(for P14), GSM53(for P21), and GSM54(for P56) as well as our homepage at http://www.brain.riken.go.jp/labs/lm Keywords = mouse cerebellum development

2010-05-27 | E-GEOD-2 | biostudies-arrayexpress

Gene expression in crossed cerebellar diaschisis in a transient middle cerebral artery occlusion rat model

Project description:Crossed cerebellar diaschisis (CCD) is hypoperfusion and hypometabolism in the contralateral cerebellar hemisphere caused by supratentorial lesion. We evaluated chronological change of cerebellar blood flow (CbBF) and gene expressions in cerebellum using a rat model of focal ischemic stroke.

2020-02-28 | GSE144547 | GEO

Gene expression data from mouse cerebellar tumor samples

Project description:Gene expression data from mouse cerebellar tumors generated using CRISPR/Cas9 technology to disrupt Ptch1 and Chd7 in the embryonic cerebellum of Chd7 fl/+ mice by in utero electroporation.

2018-08-24 | GSE72331 | GEO

A peptidomic approach to characterize peptides involved in cerebellar cortex development leads to the identification of the neurotrophic effects of nociceptin

Project description:The cerebellum is a brain structure involved in motor and cognitive functions. The development of the cerebellar cortex (the external part of the cerebellum) is under the control of numerous factors. Among these factors, neuropeptides including PACAP or somatostatin modulate the survival, migration and/or differentiation of cerebellar granule cells. Interestingly, such peptides contributing to cerebellar ontogenesis usually exhibit a specific transient expression profile with a low abundance at birth, a high expression level during the developmental processes, which take place within the first two postnatal weeks in rodents, and a gradual decline toward adulthood. Thus, to identify new peptides transiently expressed in the cerebellum during development, rat cerebella were sampled from birth to adulthood, and analyzed by a semi-quantitative peptidomic approach. A total of 33 peptides were found to be expressed in the cerebellum. Among these 33 peptides, 8 had a clear differential expression pattern during development, 4 of them i.e. cerebellin 2, nociceptin, somatostatin and VGF [353-372], exhibiting a high expression level during the first two postnatal weeks followed by a significative decrease at adulthood. A focus by a genomic approach on nociceptin, confirmed that the precursor mRNA is transiently expressed during the first week of life in granule neurons within the internal granule cell layer of the cerebellum, and showed that the nociceptin receptor is also actively expressed between P8 and P16 by the same neurons. Finally, functional studies revealed a new role for nociceptin, acting as a neurotrophic peptide able to promote the survival and differentiation of developing cerebellar granule neurons.

2018-06-15 | PXD006874 | Pride

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