Unknown,Transcriptomics,Genomics,Proteomics

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Retinoids induce rapid dynamic changes in the non-coding RNAs and epigenetic profiles of murine Hox clusters (ChIP-chip)

ABSTRACT: Physiologically relevant concentrations of retinoic acid are added to Mouse ES cells and a time course (0-72 hours) is examined with tiling array ChIP-chip and RNA-seq to characterize the early dynamics of expression of coding and non-coding RNAs and epigenetics in and around the Hox clusters. Expression, epigenetics, and RARs are examined at various timepoints (0-24hrs) after retinoic acid induced neuronal differentiation

ORGANISM(S): Mus musculus

SUBMITTER: Madelaine Gogol

PROVIDER: E-GEOD-61584 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Background Primitive brain tumors are the first cause of cancer-related death in children. Tumor cells with stem-like properties (TSCs), thought to account for tumorigenesis and therapeutic resistance, have been isolated from high-grade gliomas in adults. Whether TSCs are a common component of pediatric brain tumors and are of clinical relevance remains to be determined. Methodology/Principal findings Tumor cells with self-renewal properties were isolated with cell biology techniques from a majority of 55 pediatric brain tumors samples, regardless of their histopathologies and grades of malignancy (57% of embryonal tumors, 57% of low-grade gliomas and neuro-glial tumors, 70% of ependymomas, 91% of high-grade gliomas). The vast majority (10/12) of high-grade glioma-derived oncospheres sustained long-term self-renewal numbers akin to neural stem cells (>7 self-renewals), whereas cells with limited renewing abilities akin to neural progenitors dominated in all other tumor types. Regardless of tumor entities, the young age group was associated with self-renewal properties akin to neural stem cells (P=0.05, chi-square test). TSCs shared a complex molecular profile combining embryonic stem cell markers with elements controlling neural stem cell properties and epithelio-mesenchymal transitions. They were radio- and chemoresistant and formed aggressive tumors after intracerebral grafting. Survival analysis of the cohort showed an association between isolation of TSCs with long-term self-renewal abilities and a patients higher mortality rate (P = 0.022, log-rank test). Patients bearing cells with limited self-renewal properties constituted an intermediate group of survival but which did not reach statistical significance. Conclusions/Significance In brain tumors affecting adult patients, TSC have been isolated only from high-grade gliomas. In contrast, our data show that tumor cells with stem cell-like or progenitor-like properties can be isolated from a wide range of histological sub-types and grades of pediatric brain tumors. They suggest that cellular mechanisms fueling tumor development differ between adult and pediatric brain tumors.

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Retinoids induce rapid dynamic changes in the non-coding RNAs and epigenetic profiles of murine Hox clusters (ChIP-chip)

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