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GSE85044
Mus musculus
16 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Targeting immunomodulatory pathways has ushered a new era in lung cancer therapy. Further progress requires deeper insights into the nature and dynamics of immune cells in the lung cancer micro-environment. Dendritic cells (DCs) represent a heterogenous and highly plastic immune cell system with a central role in controlling immune responses. The intratumoral infiltration and activation status of DCs emerge as clinically relevant parameters in lung cancer. In this study we used an orthotopic preclinical model of lung cancer to interrogate the transcriptome of lung tumor-infiltrating DCs and extract novel biologically and clinically relevant information. Lung tumor-infiltrating leukocytes expressing generic DC markers were found to predominantly consist of CD11b+ cells which, compared to peritumoral lung DC counterparts, strongly over-express the T cell inhibitory molecule PD-L1 and acquire classic markers of tumor-supporting macrophages (TAM) on their surface. Transcriptome analysis of these CD11b+ tumor-infiltrating DCs (TIDCs) indicates impaired anti-tumoral immunogenicity, confirms the skewing towards TAM-related features, and indicates exposure to a hypoxic environment. In paralled, TIDCs display a specific micro-RNA signature dominated by the prototypical lung cancer oncomir miR-31. Hypoxia was found to drive intrinsic miR-31 expression in CD11b+DCs. Conditioned medium of mir-31-overexpressing CD11b+DCs induces pro-invasive lung cancer cell shape changes and is enriched with the pro-metastatic factors S100A8 and S100A9. Finally, analysis of TCGA datasets reveals that the TIDC-associated miRNA signature has a negative prognostic impact in non-small cell lung cancer. Together, these data suggest a novel mechanism through which lung cancer co-opts the plasticity of the DC system to support tumoral progression. Targeting immunomodulatory pathways has ushered a new era in lung cancer therapy. Further progress requires deeper insights into the nature and dynamics of immune cells in the lung cancer micro-environment. Dendritic cells (DCs) represent a heterogenous and highly plastic immune cell system with a central role in controlling immune responses. The intratumoral infiltration and activation status of DCs emerge as clinically relevant parameters in lung cancer. In this study we used an orthotopic preclinical model of lung cancer to interrogate the transcriptome of lung tumor-infiltrating DCs and extract novel biologically and clinically relevant information. Lung tumor-infiltrating leukocytes expressing generic DC markers were found to predominantly consist of CD11b+ cells which, compared to peritumoral lung DC counterparts, strongly over-express the T cell inhibitory molecule PD-L1 and acquire classic markers of tumor-supporting macrophages (TAM) on their surface. Transcriptome analysis of these CD11b+ tumor-infiltrating DCs (TIDCs) indicates impaired anti-tumoral immunogenicity, confirms the skewing towards TAM-related features, and indicates exposure to a hypoxic environment. In paralled, TIDCs display a specific micro-RNA signature dominated by the prototypical lung cancer oncomir miR-31. Hypoxia was found to drive intrinsic miR-31 expression in CD11b+DCs. Conditioned medium of mir-31-overexpressing CD11b+DCs induces pro-invasive lung cancer cell shape changes and is enriched with the pro-metastatic factors S100A8 and S100A9. Finally, analysis of TCGA datasets reveals that the TIDC-associated miRNA signature has a negative prognostic impact in non-small cell lung cancer. Together, these data suggest a novel mechanism through which lung cancer co-opts the plasticity of the DC system to support tumoral progression.
Publication Title
The transcriptome of lung tumor-infiltrating dendritic cells reveals a tumor-supporting phenotype and a microRNA signature with negative impact on clinical outcome.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
The nuclear receptor PPARalpha is recognized as the primary target of the fibrate class of hypolipidemic drugs and mediates lipid lowering in part by activating a transcriptional cascade that induces genes involved in the catabolism of lipids. We report here the characterization of three novel PPARalpha agonists with therapeutic potential for treating dyslipidemia. These structurally related compounds display potent and selective binding to human PPARalpha and support robust recruitment of coactivator peptides in vitro. These compounds markedly potentiate chimeric transcription systems in cell-based assays and strikingly lower serum triglycerides in vivo. The transcription networks induced by these selective PPARalpha agonists were assessed by transcriptional profiling of mouse liver after acute and chronic treatment. The induction of several known PPARalpha target genes involved with fatty acid metabolism were observed, reflecting the expected pharmacology associated with PPARalpha activation. We also noted the downregulation of a number of genes related to immune cell function, the acute phase response, and glucose metabolism; suggesting that these compounds may have anti-inflammatory action in the mammalian liver. Taken together, these studies articulate the therapeutic promise of a selective PPARalpha agonist.
Publication Title
Molecular characterization of novel and selective peroxisome proliferator-activated receptor alpha agonists with robust hypolipidemic activity in vivo.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
NextSeq 500
Description
We report the phenotype of human lung ILC2 and ILC3 populations from individuals with tuberculosis (TB) and non-TB cancer controls. We find that ILC2s demonstrate moderate transcriptional differences in TB infection, whereas ILC3s demonstrate large differences. Overall design: ILC2s and ILC3s were purified by FACS from lung biopsies from TB infected lung tissue and peripheral healthy lung tissue from individuals with cancer. Low-input RNA-seq was performed on 1-3 replicates (dependent on cell number) on 5 individuals with TB infection and 2 controls.
Publication Title
Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Affymetrix Mouse Promoter 1.0R Array (mmprompr)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The activity-dependent histone variant H2BE modulates the life span of olfactory neurons.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Promoter 1.0R Array (mmprompr), Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We have identified a replication-independent histone variant, Hist2h2be (referred to herein as H2be), which is expressed exclusively by olfactory chemosensory neurons. Levels of H2BE are heterogeneous among olfactory neurons, but stereotyped according to the identity of the co-expressed olfactory receptor (OR). Gain- and loss-of-function experiments demonstrate that changes in H2be expression affect olfactory function and OR representation in the adult olfactory epithelium. We show that H2BE expression is reduced by sensory activity and that it promotes neuronal cell death, such that inactive olfactory neurons display higher levels of the variant and shorter life spans. Post-translational modifications (PTMs) of H2BE differ from those of the canonical H2B, consistent with a role for H2BE in altering transcription. We propose a physiological function for H2be in modulating olfactory neuron population dynamics to adapt the OR repertoire to the environment.
Publication Title
The activity-dependent histone variant H2BE modulates the life span of olfactory neurons.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 183 Downloadable Samples
- Illumina Genome Analyzer II
Description
Genomic imprinting results in the preferential expression of the paternal, or maternal allele of certain genes. We have performed a genome-wide characterization of imprinting in the mouse embryonic and adult brain using F1 hybrid mice generated from reciprocal crosses of CASTEiJ and C57BL/6J mice. We also uncovered genes associated with sex specific parental effects in the adult mouse brain. Our study identified preferential selection of the maternally inherited X chromosome in glutamatergic neurons of the female cortex. Overall design: Examination of allele specific expression in the brains of reciprocal crosses of F1 hybrid mice from CASTEiJ and C57BL/6J crosses. Processed data files (GenomicAligned, SNP_calls, TranscriptomeAligned, fRNAdbAligned) and README file linked below as supplementary files.
Publication Title
Sex-specific parent-of-origin allelic expression in the mouse brain.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 86 Downloadable Samples
- Illumina HiSeq 2000
Description
We analyzed Purkinje cell transcriptome dynamics in the developing mouse cerebellum during the first three postnatal weeks, a key developmental period equivalent to the third trimester in human cerebellar development. Our study represents the first detailed analysis of developmental Purkinje cell transcriptomes and provides a valuable dataset for gene network analyses and biological questions on genes implicated in cerebellar and Purkinje cell development. Overall design: Laser capture microdissection was employed to obtain a highly enriched population of cerebellar Purkinje cells. Deep sequencing was performed on RNA isolated from 1000 Purkinje cells at five developmental timepoints (postnatal days P0, P4, P8, P14 and P21) in triplicate.
Publication Title
A gene expression signature in developing Purkinje cells predicts autism and intellectual disability co-morbidity status.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 72 Downloadable Samples
- Illumina HiSeq 2000
Description
We sought to investigate the scope of cellular and molecular changes within a mouse's olfactory system as a function of its exposure to odors emitted from members of the opposite sex. To this end, we housed mice either separated from members of the opposite sex (sex-separated) or together with members of the opposite sex (sex-combined) until six months of age and then profiled transcript levels within the main olfactory epithelium (MOE), vomeronasal organ (VNO), and olfactory bulb (OB) of the mice via RNA-seq. For each tissue type, we then analyzed gene expression differences between sex-separated males and sex-separated females (SM v SF), sex-combined males and sex-combined females (CM v CF), sex-separated females and sex-combined females (SF v CF), and sex-separated males and sex-combined males (SM v CM). Within both the MOE and VNO, we observed significantly more numerous gene expression differences between males and females when mice were sex-separated as compared to sex-combined. Chemoreceptors were highly enriched among the genes differentially expressed between males and females in sex-separated conditions, and these expression differences were found to reflect differences in the abundance of the corresponding sensory neurons. Overall design: For each combination of tissue (MOE, VNO, OB), sex (F, M), and condition (sex-separated [S], sex-combined [C]), we generated three biological replicate samples of RNA, each of which contained equal quantities of RNA from two different mice. This resulted in a total of 36 samples.
Publication Title
Sex separation induces differences in the olfactory sensory receptor repertoires of male and female mice.
Sample Metadata Fields
Sex, Age, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
Phospho-ribosome associated RNAs were immunopurified using the antibodies against phospho-S6. The purified RNAs were converted to cDNAs, which were sequenced in Illumina HiSeq platform. Vomeronasal organs were extracted from male CD-1 animals exposed to either pup cues or fresh bedding. Overall design: Total of 6 samples, 2 conditions and 3 replicates
Publication Title
Multisensory Logic of Infant-Directed Aggression by Males.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
B6D2F1 male mice at the age of 6 weeks were maintained for one week in a 12h light / 12 h dark (LD12:12) cycle (lights on from 7:00 am to 7:00 pm) and food and water ad libitum. Mice were then divided in two experimental groups which were further maintained for 3 weeks in the LD12 cycle and fed either at libitum or only during a 4 h period between 9:00 am and 1:00 pm. All animals were then implanted subcutaneously with a pancreatic P03 adenocarcinoma in both flanks. Tumour growth was monitored daily and twenty one days after innoculation, animals were transfered to constant darkness for 24h. Tumour samples were collected at the implantation site at circadian time (CT)4 and CT16.
Publication Title
Cancer inhibition through circadian reprogramming of tumor transcriptome with meal timing.
Sample Metadata Fields
Sex, Age, Specimen part, Time
View Samples