Project description:Analysis of differential gene expression in HeLa Parental vs radio-resistant xenograft tumours. The aim is to identify potential genes that are deregulated in radio-resistant tumours.
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.
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
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.
Project description:Embryonic genome activation (EGA) marks the onset of embryonic program and enables the transition toward the first lineage specification. However, the molecular features of EGA and the transcription factors (TFs) orchestrating this process remain unclear. Here, by performing single-cell RNA-seq on bovine embryos, we reveal that major EGA is asynchronously initiated among blastomeres at the 8-cell stage. Integrative analyses reveal distinctive protein accumulation compared to transcription and translation activation during bovine EGA. Furthermore, we investigate the role of SP1, a TF activated at the minor EGA stage, with motifs enriched in accessible chromatin during major EGA stage in bovine and human embryos. SP1 deficiency leads to morula arrest in bovine and impairs EGA in human embryos. Multi-omics analysis demonstrates that SP1 promotes early lineage gene expression by modulating nearby chromatin states in bovine and directly targets key EGA genes in human embryos. Together, our study delineates the dynamics of bovine EGA and uncovers the conserved and species-specific roles of SP1 in regulating EGA and early development in mammals.
Project description:Arrested bone marrow (BM) lymphoid cell differentiation underlies the emergence of the most common childhood cancer, acute lymphoblastic leukemia (ALL). Recurrent genetic lesions often directly involve transcription factors (TFs), such as ETV6 and RUNX1 found in the most common ALL translocation. Here, we studied differential gene expression in ETV6-RUNX1 primary ALL samples and the REH cell line using single cell RNA-seq (scRNA-seq). Submitter declares that the raw data will be deposited in EGA due to patient privacy concerns. The raw data can be accessed at https://www.ebi.ac.uk/ega/studies/EGAS00001004374