Aberrant splice variants are involved in the initiation and/or progression of glial brain tumors. We therefore set out to identify splice variants that are differentially expressed between histological subgroups of gliomas. Splice variants were identified using a novel platform that profiles the expression of virtually all known and predicted exons present in the human genome. Exon-level expression profiling was performed on 26 glioblastomas, 22 oligodendrogliomas and 6 control brain samples. Our results demonstrate that Human Exon arrays can identify subgroups of gliomas based on their histological appearance and genetic aberrations. We next used our expression data to identify differentially expressed splice variants. In two independent approaches, we identified 49 and up to 459 exons that are differentially spliced between glioblastomas and oligodendrogliomas a subset of which (47% and 33%) were confirmed by RT-PCR. In addition, exon-level expression profiling also identified >700 novel exons. Expression of ~67% of these candidate novel exons was confirmed by RT-PCR. Our results indicate that exon-level expression profiling can be used to molecularly classify brain tumor subgroups, can identify differentially regulated splice variants and can identify novel exons. The splice variants identified by exon-level expression profiling may help to detect the genetic changes that cause or maintain gliomas and may serve as novel treatment targets.
Identification of differentially regulated splice variants and novel exons in glial brain tumors using exon expression arrays.
No sample metadata fields
View SamplesStem and progenitor cells are the critical units for tissue maintenance, regeneration, and repair. The activation of regenerative events in response to tissue injury has been correlated with mobilization of tissue-resident progenitor cells, which is functional to the wound healing process. However, until now there has been no evidence for the presence of cells with a healing capacity circulating in healthy conditions. We identified a rare cell population present in the peripheral blood of healthy mice that actively participates in tissue repair. These Circulating cells, with a Homing ability and involved in the Healing process (CH cells), were identified by an innovative flowcytometry strategy as small cells not expressing CD45 and lineage markers. Their transcriptome profile revealed that CH cells are unique and present a high expression of key pluripotency- and epiblast-associated genes. More importantly, CH-labeled cells derived from healthy Red Fluorescent Protein (RFP)-transgenic mice and systemically injected into syngeneic fractured wild-type mice migrated and engrafted in wounded tissues, ultimately differentiating into tissue-specific cells. Accordingly, the number of CH cells in the peripheral blood rapidly decreased following femoral fracture. These findings uncover the existence of constitutively circulating cells that may represent novel, accessible, and versatile effectors of therapeutic tissue regeneration.
Identification of a New Cell Population Constitutively Circulating in Healthy Conditions and Endowed with a Homing Ability Toward Injured Sites.
Sex, Specimen part
View SamplesWe co-isolated hair follicle placode and dermal condensate cells along with other specific cell types from E14.5 embryonic mouse skin. With next-generation RNA-sequencing we defined gene expression patterns in the context of the entire embryonic skin. Overall design: FACS was used to isolate specific cell types from E14.5 embryonic mouse skin.
An Integrated Transcriptome Atlas of Embryonic Hair Follicle Progenitors, Their Niche, and the Developing Skin.
No sample metadata fields
View SamplesBreast cancer is the most common cancer in women worldwide and metastatic dissemination is the principal factor related to death by this disease. Breast cancer stem cells, are thought to be responsible for metastasis and chemoresistance.. In this study, based on whole transcriptome analysis from putative breast CSCs and reverse-engineering of transcription control networks, we were able to identify two networks associated to this phenotype.
Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype.
Age, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cell-Cycle-Targeting MicroRNAs as Therapeutic Tools against Refractory Cancers.
Specimen part, Cell line
View SamplesCyclins and cyclin-dependent kinases (CDKs) are hyperactivated in nearly all human tumor types. To identify new approaches for interfering with cyclins/CDKs, we systematically searched for microRNAs (miRNAs) regulating these proteins. We uncovered a group of miRNAs that target nearly all cyclins and CDKs, and demonstrated that these miRNAs are very effective in shutting off cancer cell expansion. By profiling the response of over 120 human cancer cell lines representing 12 tumor types to these cell-cycle-targeting miRNAs, we identified miRNAs particularly effective against triple-negative breast cancers and KRAS-mutated cancers. We also derived expression-based algorithm that predicts response of primary tumors to cell-cycle-targeting miRNAs. Using systemic administration of nanoparticle-formulated miRNAs, we halted tumor progression in seven mouse xenograft models, including three highly aggressive and treatment-refractory patient-derived tumors, without affecting normal tissues. Our results highlight the utility of using cell-cycle-targeting miRNAs for treatment of refractory cancer types. Overall design: RNA-seq for SW900 cells transfected with 25 nM of miR-193a-3p mimic or 25 nM of negative miRNA control (Negative control #2, Ambion).
Cell-Cycle-Targeting MicroRNAs as Therapeutic Tools against Refractory Cancers.
No sample metadata fields
View SamplesCyclins and cyclin-dependent kinases (CDKs) are hyperactivated in nearly all human tumor types. To identify new approaches for interfering with cyclins/CDKs, we systematically searched for microRNAs (miRNAs) regulating these proteins. We uncovered a group of miRNAs that target nearly all cyclins and CDKs, and demonstrated that these miRNAs are very effective in shutting off cancer cell expansion. By profiling the response of over 120 human cancer cell lines representing 12 tumor types to these cell-cycle-targeting miRNAs, we identified miRNAs particularly effective against triple-negative breast cancers and KRAS-mutated cancers. We also derived expression-based algorithm that predicts response of primary tumors to cell-cycle-targeting miRNAs. Using systemic administration of nanoparticle-formulated miRNAs, we halted tumor progression in seven mouse xenograft models, including three highly aggressive and treatment-refractory patient-derived tumors, without affecting normal tissues. Our results highlight the utility of using cell-cycle-targeting miRNAs for treatment of refractory cancer types.
Cell-Cycle-Targeting MicroRNAs as Therapeutic Tools against Refractory Cancers.
Specimen part
View SamplesThe retinoblastoma tumor suppressor protein (Rb) regulates early G1 phase checkpoints, including the DNA damage response, as well as cell cycle exit and differentiation. The widely accepted model of G1 cell cycle progression proposes that cyclin D:Cdk4/6 partially inactivates the Rb tumor suppressor during early G1 phase by progressive multi-phosphorylation, termed hypo-phosphorylation, resulting in release of E2F transcription factors. However, this model remains largely unproven biochemically and the biologically active form(s) of Rb remains unknown. Here we find that Rb is un-phosphorylated in G0 cells and becomes exclusively mono-phosphorylated throughout all of early G1 phase by cyclin D:Cdk4/6. Early G1 phase mono-phosphorylated Rb is composed of 14 independent isoforms that are all targeted by the E1a oncoprotein, but each shows a preferential binding pattern to specific E2F1-4 transcription factors. At the late G1 Restriction Point, cyclin E:Cdk2 inactivates Rb by a quantum hyper-phosphorylation (>12 phosphates/Rb). Cells undergoing a DNA damage response activate cyclin D:Cdk4/6 to generate mono-phosphorylated Rb that regulates global transcription. In contrast, a non-phosphorylatable ?Cdk-Rb allele was non-functional for regulating a DNA damage response, but functional for driving cell cycle exit and differentiation during myogenesis. These observations fundamentally change our understanding of G1 cell cycle progression and show that there is no progressive multi-phosphorylation or hypo-phosphorylation inactivation of Rb during early G1 phase by cyclin D:Cdk4/6. Instead, cyclin D:Cdk4/6 generates functionally active, mono-phosphorylated Rb that is the only Rb isoform present in cells during early G1 phase.
Cyclin D activates the Rb tumor suppressor by mono-phosphorylation.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
c-Jun promotes cell migration and drives expression of the motility factor ENPP2 in soft tissue sarcomas.
Specimen part, Cell line
View SamplesAffymetrix exon arrays to identify genes that were differentially expressed after c-Jun inhibition in LPS cell line with and with no Jun amplification.
c-Jun promotes cell migration and drives expression of the motility factor ENPP2 in soft tissue sarcomas.
Specimen part, Cell line
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