Inactivating mutations in SMARCA4 (BRG1), a key SWI/SNF chromatin remodelling gene, underlie small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). To reveal its druggable vulnerabilities, we perform kinase-focused RNAi screens and uncover that SMARCA4-deficient SCCOHT cells are highly sensitive to the inhibition of cyclin-dependent kinase 4/6 (CDK4/6). SMARCA4 loss causes profound downregulation of cyclin D1, which limits CDK4/6 kinase activity in SCCOHT cells and leads to in vitro and in vivo susceptibility to CDK4/6 inhibitors. SCCOHT patient tumors are deficient in cyclin D1 yet retain the retinoblastoma-proficient/p16INK4a-deficient profile associated with positive responses to CDK4/6 inhibitors. Thus, our findings indicate that CDK4/6 inhibitors, approved for a breast cancer subtype addicted to CDK4/6 activation, could be repurposed to treat SCCOHT. Moreover, our study suggests a novel paradigm whereby critically low oncogene levels, caused by loss of a driver tumor suppressor, may also be exploited therapeutically. Overall design: The effect of CDK6 knockdown and palbociclib treatment on SCCOHT cells.
CDK4/6 inhibitors target SMARCA4-determined cyclin D1 deficiency in hypercalcemic small cell carcinoma of the ovary.
Specimen part, Treatment, Subject
View SamplesExcessive accumulation of lipids in the adipose tissue is a major problem in the present-day broiler industry. However, few studies have analyzed the expression of adipose tissue genes that are involved in pathways and mechanisms leading to adiposity in chickens. Gene expression profiling of chicken adipose tissue could provide key information about the ontogenesis of fatness and clarify the molecular mechanisms underlying obesity.
Profiling of chicken adipose tissue gene expression by genome array.
Age
View SamplesCutaneous CD30+ lymphoproliferative disorder (CD30+LPDs), including lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large-cell lymphoma (PCALCL), comprises the second most common group of cutaneous T cell lymphoma. Previously, we reported that special AT-rich sequence-binding protein1 (SATB1), a thymocyte specific chromatin organizer, was over-expressed and promoted malignant T-cell proliferation in a portion of CD30+LPDs, whereas other CD30+LPDs didn't express SATB1 at all. To elucidate the underlying molecular events in CD30+LPDs with differential SATB1 expression, we subjected 4 SATB1+ and 3 SATB1- CD30+LPDs skin biopsies to second-generation RNA-sequencing (RNA-seq). These data provide a significant resource for studies of CD30+LPDs. Overall design: 200ng total RNA samples were extracted and purified from 7 CD30+LPDs skin lesions (4 SATB1+, 3 SATB1-) to establish RNA library. Then the library was qualified through Agilent 2100 bioanalyzer instrument (Agilent Technologies, Santa Clara, CA) and Quantitative real-time polymerase chain reaction. The qualified library was sequenced on an Illumina HiSeqTM 2000 platform using paired-end reads. 10G raw data for each sample were obtained. The reads were aligned to the hg19 genome with SOAPaligner/SOAP2. Gene expression levels were calculated by reads per kilobase transcriptome per million mapped reads(RPKM)method.
SATB1 Defines a Subtype of Cutaneous CD30<sup>+</sup> Lymphoproliferative Disorders Associated with a T-Helper 17 Cytokine Profile.
Specimen part, Subject
View SamplesGlioblastoma (GBM) is the most common and aggressive primary brain tumor in adults, with glioma initiating cells (GICs) implicated to be critical for tumor progression and resistance to therapy. KDM1B is involved in regulating GICs'' responses to hypoxia, since over-expression of KDM1B delays the cell growth under hypoxia while knocking-down of KDM1B in GICs promotes their survival and tumorigenic abilities. Overall design: We used RNA-Sequencing to detail the global change of gene expression in GICs with knockdown of KDM1B, and identified de-regulated genes and pathways downstream of KDM1B. CD133+ D456MG GICs were infected with non-targeting control and shRNA of KDM1B. Then RNA was extracted and gene expression was profiled by RNA-Seq.
MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B.
No sample metadata fields
View SamplesSolar ultraviolet CUV-Cradiation reaching the Earths surface is little due to the filtering effects of the stratospheric ozone layer. At present, artificial UV-C irradiation is utilized for different biological processes. Grape is a major fruit crop around the world. Research has shown that UV-C irradiation induced the biosynthesis of phenols. However, changes at the molecular level in response to UV-C and leading to these effects are poorly understood. To elucidate the effect of UV-C on expression of genes in grape and the response mechanism, transcript abundance of grape (Vitis vinifera L.) leaves was quantified using the Affymetrix Grape Genome oligonucleotide microarray (15,700 transcripts)
Transcriptomic analysis of grape (Vitis vinifera L.) leaves after exposure to ultraviolet C irradiation.
Age, Treatment
View SamplesAlthough the well-known importance of pig in agriculture, as well as a model for human biology, the miRNA catalog of pig has been largely undefined. Identification and preliminary characterization of adipose- and muscle-specific miRNAs would be a prerequisite for a thorough understanding of their roles in regulating adipose deposition and muscle growth. In the present study, we get insight into the miRNA transcriptome in eight adipose tissues, two skeletal muscles and cardiac muscle of pig using deep sequencing technology, and to elucidate their characteristic tissue-specific profiles and genomic context. Overall design: Eleven small RNA libraries from eight adipose tissues, two skeletal muscle tissues and cardiac muscle of pig were sequenced.
An atlas of DNA methylomes in porcine adipose and muscle tissues.
Sex, Age, Specimen part, Subject
View SamplesHaploid pluripotent stem cells, such as haploid embryonic stem cells (haESCs), facilitate the genetic study of recessive traits. In vitro, fish haESCs maintain haploidy in both undifferentiated and differentiated states, but whether mammalian haESCs can preserve pluripotency in the haploid state has not been tested. Here, we report that mouse haESCs can differentiate in vitro into haploid epiblast stem cells (haEpiSCs), which maintain an intact haploid genome, unlimited self-renewal potential, and durable pluripotency to differentiate into various tissues in vitro and in vivo. Mechanistically, the maintenance of self-renewal potential depends on the Activin/bFGF pathway. We further show that haEpiSCs can differentiate in vitro into haploid progenitor-like cells.
Durable pluripotency and haploidy in epiblast stem cells derived from haploid embryonic stem cells in vitro.
Specimen part
View SamplesOur study revealed photoperiod influenced on not only flowering not only stress responses under long-day conditions and ZmCCT and ZmCCA1 were the key functional links between the circadian clock and adversity stress tolerance. Establishment of the molecular link reveals a new interface between the plant phtoperiod and adversity stress.
Dual functions of the ZmCCT-associated quantitative trait locus in flowering and stress responses under long-day conditions.
Specimen part
View SamplesRNA-seq analysis of Rcor2fl/fl and Rcor2cko embryonic cortex. Overall design: we dissected VZ-SVZ regions of Rcor2fl/fl and Rcor2cko cortex at E13.5 and E15.5 for RNA-seq respectively.
LSD1 co-repressor Rcor2 orchestrates neurogenesis in the developing mouse brain.
Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative microRNA-gene expression network analysis in genetic hypercalciuric stone-forming rat kidney.
Sex, Specimen part, Disease, Disease stage
View Samples