We compare whole-animal RNA-seq transcriptomes for C. elegans males and hermaphrodites from the late L3 larval stage to young adulthood. During this interval, male sexual structures develop, including extensive neurogenesis and synaptogenesis that nearly doubles the size of the nervous system. Previous genome-wide expression studies in C. elegans have usually focused on only one sex – the hermaphrodite, and there are a relatively large number of predicted genes that still remain without meaningful annotation. In the present study, differential expression analysis of the RNA-seq data revealed 1,751 genes expressed at a higher level in the male. By differential expression analysis, unbiased gene correlation analysis, and a guilt-by-association approach, we identified new transcription factors required for differentiation of male genital structures, semen proteins, and candidates for previously-unknown components for synapse function. The results validate the dataset as a rich resource for future gene discovery in C. elegans. Overall design: To analyze gene expression during sexual maturation in C. elegans, we performed RNA-seq for five samples for each sex ranging at 6 hr intervals from late L3 to young adult stages
Gene Function Prediction Based on Developmental Transcriptomes of the Two Sexes in C. elegans.
Sex, Subject, Time
View SamplesTumor-stromal communication within the microenvironment contributes to initiation of metastasis and may present a therapeutic opportunity. Using serial single cell RNA-sequencing in an orthotopic mouse prostate cancer model, we find upregulation of Prolactin receptor as cancer cells that have disseminated to the lung expand into micrometastases. Secretion of the ligand Prolactin by adjacent lung stromal cells is induced by tumor cell production of the COX-2 synthetic product prostaglandin E-2 (PGE-2). PGE-2 treatment of fibroblasts activates the nuclear orphan receptor NR4A (Nur77), with Prolactin as a major transcriptional target for the NR4A-Retinoid X receptor (RXR) heterodimer. Ectopic expression of Prolactin receptor in mouse cancer cells enhances micrometastasis, while treatment with the COX-2 inhibitor Celecoxib abrogates Prolactin secretion by fibroblasts and reduces tumor initiation. Across multiple human cancers, COX-2, Prolactin, and Prolactin receptor show consistent differential expression in tumor and stromal compartments. Such paracrine crosstalk may thus contribute to the documented efficacy of COX-2 inhibitors in cancer suppression. Overall design: Primary tumors were established by direct prostate inoculation into immunosuppressed NSG mice of CE1-4 prostate cancer cells, derived from tissue-specific inactivation of PTEN [Pubmed ID: 20631921]. These cells, which were GFP-luciferase tagged, are noteworthy in that they have preserved expression of the androgen receptor and epithelial markers and recapitulate biological features of human prostate cancer. Six weeks following intra-prostate inoculation, multiple single DTCs were identified microscopically within the lungs (394 cells/hpf), with a smaller number in liver (54 cells/hpf), brain (9 cells/hpf) and bone marrow (1 cell/hpf). To undertake RNA sequencing of single cells during progression from quiescent DTCs to proliferative lesions, we identified GFP-tagged single tumor cells from lung harvested at various intervals, analyzing these separately from microdissected multicellular lesions. Individual DTCs collected at 6-7 weeks (DTC-I; N=20) and at 9-11 weeks (DTC-II; N=55) were compared with single cells derived from the primary tumor (N=29), lung micro-metastases (N=33), and CTCs isolated by microfluidic capture from blood specimens (N=12) [Pubmed ID: 28181495].
COX-2 mediates tumor-stromal prolactin signaling to initiate tumorigenesis.
Disease, Subject
View SamplesTumor-stromal communication within the microenvironment contributes to initiation of metastasis and may present a therapeutic opportunity. Using serial single cell RNA-sequencing in an orthotopic mouse prostate cancer model, we find upregulation of Prolactin receptor as cancer cells that have disseminated to the lung expand into micrometastases. Secretion of the ligand Prolactin by adjacent lung stromal cells is induced by tumor cell production of the COX-2 synthetic product prostaglandin E-2 (PGE-2). PGE-2 treatment of fibroblasts activates the nuclear orphan receptor NR4A (Nur77), with Prolactin as a major transcriptional target for the NR4A-Retinoid X receptor (RXR) heterodimer. Ectopic expression of Prolactin receptor in mouse cancer cells enhances micrometastasis, while treatment with the COX-2 inhibitor Celecoxib abrogates Prolactin secretion by fibroblasts and reduces tumor initiation. Across multiple human cancers, COX-2, Prolactin, and Prolactin receptor show consistent differential expression in tumor and stromal compartments. Such paracrine crosstalk may thus contribute to the documented efficacy of COX-2 inhibitors in cancer suppression. Overall design: We performed RNA-seq on the human dermal fibroblast cell line DF treated for six hours with PGE-2 or untreated.
COX-2 mediates tumor-stromal prolactin signaling to initiate tumorigenesis.
Specimen part, Cell line, Treatment, Subject
View SamplesTumor-stromal communication within the microenvironment contributes to initiation of metastasis and may present a therapeutic opportunity. Using serial single cell RNA-sequencing in an orthotopic mouse prostate cancer model, we find upregulation of Prolactin receptor as cancer cells that have disseminated to the lung expand into micrometastases. Secretion of the ligand Prolactin by adjacent lung stromal cells is induced by tumor cell production of the COX-2 synthetic product prostaglandin E-2 (PGE-2). PGE-2 treatment of fibroblasts activates the nuclear orphan receptor NR4A (Nur77), with Prolactin as a major transcriptional target for the NR4A-Retinoid X receptor (RXR) heterodimer. Ectopic expression of Prolactin receptor in mouse cancer cells enhances micrometastasis, while treatment with the COX-2 inhibitor Celecoxib abrogates Prolactin secretion by fibroblasts and reduces tumor initiation. Across multiple human cancers, COX-2, Prolactin, and Prolactin receptor show consistent differential expression in tumor and stromal compartments. Such paracrine crosstalk may thus contribute to the documented efficacy of COX-2 inhibitors in cancer suppression. Overall design: We performed RNA-seq on the mouse prostate cancer cell line CE1-4 treated for six hours with PGE-2 or untreated.
COX-2 mediates tumor-stromal prolactin signaling to initiate tumorigenesis.
Specimen part, Cell line, Treatment, Subject
View SamplesAvian coccidiosis is a major disease of poultry caused by the intestinal protozoa Eimeria. Aviagen line A and line B birds show differential susceptibility to Eimeria infection, with line B birds exhibiting higher lesion scores and mortality. The objective of this study was to examine differential intestinal gene expression between line A and B chicks in response to a challenge with Eimeria maxima. Following challenge with 1 x 10^4 oocysts/chick, greater than 40% of line A chicks had lesion scores of 0 to 1 (on 0 to 4 scale), similar to controls. In contrast, all line B challenged chicks at this same dose had lesion scores of 2 to 4.
An antimicrobial peptide is downregulated in the small intestine of Eimeria maxima-infected chickens.
Specimen part
View SamplesBy using high-density DNA microarrays, we analyzed the gene-expression profile of SHSY5Y neuroblastoma cells after treatment with cobalt chloride
Investigation of Endogenous Retrovirus Sequences in the Neighborhood of Genes Up-regulated in a Neuroblastoma Model after Treatment with Hypoxia-Mimetic Cobalt Chloride.
Specimen part, Cell line
View SamplesWe microdissected discrete sub-regions of esophageal squamous cell carcinoma (ESCC) and analyzed the transcriptomes throughout three-dimensional (3D) tumor space.
Identification of unique expression signatures and therapeutic targets in esophageal squamous cell carcinoma.
Specimen part, Disease
View SamplesWe utilized tissue microdissection and expression microarrays to measure ex vivo gene expression profiles in twelve cases of patient-matched normal basal epithelial cells, normal differentiated squamous epithelium, and cancer.
Identification of unique expression signatures and therapeutic targets in esophageal squamous cell carcinoma.
Specimen part, Disease
View SamplesMS-275 and hydroxyurea treatment influences whole gene expression including DNA damage response and cell cycle checkpoint signaling.
HDAC1 and HDAC2 integrate checkpoint kinase phosphorylation and cell fate through the phosphatase-2A subunit PR130.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
GENE REGULATION. Discrete functions of nuclear receptor Rev-erbα couple metabolism to the clock.
Specimen part, Time
View Samples