MAGIC_RNA-Seq_MBs_bulkRNAseq_A_ids - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001004435 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Childhood Cerebellar Tumors Mirror Conserved Fetal Transcriptional Programs
| PRJNA484319 | ENA
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
Project description:Copy number analysis of 21 paediatric low-grade astrocytomas identified a discrete copy number gain of 1.9Mb in chromosome band 7q34. The gain was present in 12/14 cerebellar pilocytic astrocytomas. Subsequent analysis of tumour cDNA indentified a novel gene fusion between KIAA1549 and BRAF in these tumours.
2009-04-16 | GSE14960 | GEO
Project description:Embryonal tumours of the central nervous system (CNS) represent a heterogeneous group of tumours about which little is known biologically, and whose diagnosis, on the basis of morphologic appearance alone, is controversial. Medulloblastomas, for example, are the most common malignant brain tumour of childhood, but their pathogenesis is unknown, their relationship to other embryonal CNS tumours is debated, and patients' response to therapy is difficult to predict. We approached these problems by developing a classification system based on DNA microarray gene expression data derived from 99 patient samples. Here we demonstrate that medulloblastomas are molecularly distinct from other brain tumours including primitive neuroectodermal tumours (PNETs), atypical teratoid/rhabdoid tumours (AT/RTs) and malignant gliomas. Previously unrecognized evidence supporting the derivation of medulloblastomas from cerebellar granule cells through activation of the Sonic Hedgehog (SHH) pathway was also revealed. We show further that the clinical outcome of children with medulloblastomas is highly predictable on the basis of the gene expression profiles of their tumours at diagnosis.
2015-05-16 | GSE68956 | GEO
Project description:Embryonal tumours of the central nervous system (CNS) represent a heterogeneous group of tumours about which little is known biologically, and whose diagnosis, on the basis of morphologic appearance alone, is controversial. Medulloblastomas, for example, are the most common malignant brain tumour of childhood, but their pathogenesis is unknown, their relationship to other embryonal CNS tumours is debated, and patients' response to therapy is difficult to predict. We approached these problems by developing a classification system based on DNA microarray gene expression data derived from 99 patient samples. Here we demonstrate that medulloblastomas are molecularly distinct from other brain tumours including primitive neuroectodermal tumours (PNETs), atypical teratoid/rhabdoid tumours (AT/RTs) and malignant gliomas. Previously unrecognized evidence supporting the derivation of medulloblastomas from cerebellar granule cells through activation of the Sonic Hedgehog (SHH) pathway was also revealed. We show further that the clinical outcome of children with medulloblastomas is highly predictable on the basis of the gene expression profiles of their tumours at diagnosis. golub-00460 Assay Type: Gene Expression Provider: Affymetrix Array Designs: Hu6800 Organism: Homo sapiens (ncbitax) Material Types: synthetic_RNA, organism_part, whole_organism, total_RNA Disease States: synthetic_RNA, organism_part, whole_orMedulloblastoma, renal rhabdoid tumor, Atypical Teratoid/Rhabdoid Tumor, Supratentorial PNET, Supratentorial PNET (pineoblastoma), Normal, Malignant Glioma, Extrarenal Rhabdoid Tumorganism, total_RNA
2015-05-16 | E-GEOD-68956 | biostudies-arrayexpress
Project description:Copy number analysis of 21 paediatric low-grade astrocytomas identified a discrete copy number gain of 1.9Mb in chromosome band 7q34. The gain was present in 12/14 cerebellar pilocytic astrocytomas. Subsequent analysis of tumour cDNA indentified a novel gene fusion between KIAA1549 and BRAF in these tumours. Copy number analysis of 21 paediatric low-grade astrocytomas using the Affymetrix GeneChip Human Mapping 250K Nsp Array. This study comprised 14 pilocytic astrocytomas, 4 diffuse astrocytomas, one pilomyxoid astrocytoma, one pilomyxoid glioma and one pleomorphic xanthoastrocytoma. Tumours were compared to the mean of two normal male DNA controls.
2010-04-09 | E-GEOD-14960 | biostudies-arrayexpress
Project description:Medulloblastoma is a malignant childhood cerebellar tumour comprised of distinct molecular subgroups. Whereas genomic characteristics of these subgroups are well defined, the extent to which cellular diversity underlies their divergent biology and clinical behaviour remains largely unexplored. We used single-cell transcriptomics to investigate intra- and inter-tumoural heterogeneity in twenty-five medulloblastomas spanning all molecular subgroups. WNT, SHH, and Group 3 tumours comprised subgroup-specific undifferentiated and differentiated neuronal-like malignant populations, whereas Group 4 tumours were exclusively comprised of differentiated neuronal-like neoplastic cells. SHH tumours closely resembled granule neurons of varying differentiation states that correlated with patient age. Group 3 and Group 4 tumours exhibited a developmental trajectory from primitive progenitor-like to more mature neuronal-like cells, whose relative proportions distinguished these subgroups. Cross-species transcriptomics defined distinct glutamatergic populations as putative cells-of-origin for SHH and Group 4 subtypes. Collectively, these data provide novel insights into the cellular and developmental states underlying subtype-specific medulloblastoma biology.
2019-07-30 | GSE119926 | GEO
Project description:Although 90% of children with acute lymphoblastic leukemia (ALL) are now cured, the prognosis of infant-ALL (diagnosis within the first year of life) remains dismal. Infant-ALL is usually caused by a single genetic hit that arises in utero: rearrangement of the MLL/KMT2A gene (MLL-r). This is sufficient to give rise to a uniquely aggressive and treatment-refractory leukemia compared to older children with the same MLL-r. The reasons for disparate outcomes in patients of different ages with identical molecular drivers are unknown. This paper addresses the hypothesis that fetal-specific gene expression programs co-operate with MLL-AF4 to initiate and maintain infant-ALL. Using direct comparison of fetal and adult HSC and progenitor transcriptomes we identify fetal-specific gene expression programs in primary human cells. We show that MLL-AF4-driven infant-ALL, but not MLL-AF4 childhood-ALL, displays expression of fetal-specific genes. In a direct test of this observation, we find that CRISPR-Cas9 gene editing of primary human fetal liver cells (to produce a t(4;11)/MLL-AF4 translocation) replicates the clinical features of infant-ALL and drives infant-ALL-specific and fetal-specific gene expression programs. These data strongly support the hypothesis that fetal-specific gene expression programs co-operate with MLL-AF4 to initiate and maintain the distinct biology of infant ALL.
2021-10-25 | GSE162034 | GEO
Project description:This cohort is an extension of our previous dataset (Spiers et al) containing DNA methylation profiled with the EPIC array on an additional 40 human fetal brain samples. Please note that these samples are from the same cohort as GSE58885.
2021-06-30 | GSE157908 | GEO
Project description:Pancreatic islet cells derived from human pluripotent stem cells hold great promise for modeling and treating diabetes. Differences between stem cell-derived and primary islets remain, but molecular insights to inform improvements are limited. Here, we acquire single-cell transcriptomes and accessible chromatin profiles during in vitro islet differentiation and from primary childhood and adult pancreas for comparison. We delineate major cell types, define their regulomes, and describe spatiotemporal regulatory relationships between transcription factors. CDX2 emerged as a regulator of enterochromaffin-like cells, which we show resemble a previously unrecognized, transient CDX2-expressing β-cell-related population in fetal pancreas, arguing against a non-pancreatic origin as proposed. Furthermore, we observe insufficient activation of signal-dependent transcriptional programs during in vitro β-cell maturation and identify sex hormones as drivers of childhood β-cell proliferation. Altogether, our analysis provides a comprehensive understanding of cell fate acquisition in stem cell-derived islets and a framework for manipulating cell identities and maturity.
2023-03-02 | GSE202498 | GEO