We established a novel EGFP reporter mouse line (named Tg(ETAR-EGFP)14Imeg), which enables the placode-derived inner ear sensory cell lineage to be visualized and monitored. At E10.5, EGFP expression was detected in the ventral and dorsomedial region of the otocyst.
Establishment of mice expressing EGFP in the placode-derived inner ear sensory cell lineage and FACS-array analysis focused on the regional specificity of the otocyst.
Specimen part
View SamplesPurpose: The goals of this study are to determine the differentially expreseed non-coding RNAs during human erythropoiesis Methods:gene expression profiling with cells on days 4,8,11,14 during erythroid differentiation, with two replicated using Illumina Genome Analyzer IIx. qRT–PCR validation was performed using TaqMan and SYBR Green assays. Conclusions: ncRNAs were differentially expressed during erythroid differentiation Overall design: mRNA profiles of day4,8,11,14 erythroid cells were generated by deep sequencing, in duplicate.
Long non-coding RNA-dependent mechanism to regulate heme biosynthesis and erythrocyte development.
Specimen part, Subject
View SamplesPurpose: The goals of this study are to determine possible downstream targets of UCA1 on day8 of erythroid differentiation with or without UCA1 knockdown. Methods:gene expression profiling with or without UCA1 knockdown in differentiated erythroblasts at day8 were generated by deep sequencing, induplicate, using Illumina GAIIx.The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT–PCR validation was performed using TaqMan and SYBR Green assays. Conclusions: heme metabolism genes were down-regulated after UCA1 knockdown during erythroid differentiation Overall design: mRNA profiles of day8 erythroid cells with or without UCA1 knockdown were generated by deep sequencing, in duplicate, using Illumina GAIIx.
Long non-coding RNA-dependent mechanism to regulate heme biosynthesis and erythrocyte development.
Specimen part, Treatment, Subject, Time
View SamplesOptimal treatment for nonalcoholic steatohepatitis (NASH) has not yet been established, particularly for individuals without diabetes.
Metformin prevents and reverses inflammation in a non-diabetic mouse model of nonalcoholic steatohepatitis.
Specimen part
View SamplesThe biologic basis for NSCLC metastasis is not well understood. Here we addressed this deficiency by transcriptionally profiling tumors from a genetic mouse model of human lung adenocarcinoma that develops metastatic disease owing to the expression of K-rasG12D and p53R172H. As a tool to investigate the biologic basis for metastasis in this model and to query the roles of specific genes in this signature, we isolated adenocarcinoma cell lines from these mice and used them to develop a syngeneic tumor model in wild-type littermates. Transcriptional profiling of the highly metastatic subcutaneous tumors revealed genes that regulate, among other processes, epithelial-to-mesenchymal transition and intra-tumoral inflammation and angiogenesis, whereas the non-metastatic tumors did not.
Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression.
No sample metadata fields
View SamplesMetastatic disease is a primary cause of cancer-related death, and factors governing tumor cell metastasis have not been fully elucidated. Here we addressed this question by using tumor cell lines derived from mice that develop metastatic lung adenocarcinoma owing to expression of mutant K-ras and p53. A feature of metastasis-prone tumor cells that distinguished them from metastasis-incompetent tumor cells was plasticity in response to changes in their microenvironment. They transited reversibly between epithelial and mesenchymal states, forming highly polarized epithelial spheres in 3-dimensional culture that underwent epithelial-mesenchymal transition (EMT) following treatment with transforming growth factor-beta or injection into syngeneic mice. This plasticity was entirely dependent upon the microRNA-200 family, which decreased during EMT. Forced expression of miR-200 abrogated the capacity of these tumor cells to undergo EMT, invade, and metastasize and conferred transcriptional features of metastasis-incompetent tumor cells. We conclude that microenvironmental cues direct tumor metastasis by regulating miR-200 expression.
Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Expression signatures of metastatic capacity in a genetic mouse model of lung adenocarcinoma.
No sample metadata fields
View SamplesThe biologic basis for NSCLC metastasis is not well understood. Here we addressed this deficiency by transcriptionally profiling tumors from a genetic mouse model of human lung adenocarcinoma that develops metastatic disease owing to the expression of K-rasG12D and p53R172H. We identified 2,209 genes that were differentially expressed in distant metastases relative to matched lung tumors. Mining of publicly available data bases revealed this expression signature in a subset of NSCLC patients who had a poorer prognosis than those without the signature.
Expression signatures of metastatic capacity in a genetic mouse model of lung adenocarcinoma.
No sample metadata fields
View SamplesTumor cells that give rise to metastatic disease are a primary cause of cancer-related death and have not been fully elucidated in patients with lung cancer. Here, we addressed this question by using tissues from a mouse that develops metastatic lung adenocarcinoma owing to expression of mutant K-ras and p53. We identified a metastasis-prone population of tumor cells that differed from those with low metastatic capacity on the basis of having sphere-forming capacity in Matrigel cultures, increased expression of CD133 and Notch ligands, and relatively low tumorigenicity in syngeneic mice. Knockdown of jagged1 or pharmacologic inhibition of its downstream mediator phosphatidylinositol 3-kinase abrogated the metastatic but not the tumorigenic activity of these cells. We conclude from these studies on a mouse model of lung adenocarcinoma that CD133 and Notch ligands mark a population of metastasis-prone tumor cells and that the efficacy of Notch inhibitors in metastasis prevention should be explored.
The Notch ligand Jagged2 promotes lung adenocarcinoma metastasis through a miR-200-dependent pathway in mice.
Specimen part
View SamplesThe Zeb1 transcriptional repressor plays a key role in metastasis through the down-regulation of genes that are strong inducers of epithelial differentiation and inhibitors of stem-ness. Here we report that Zeb1 controls the expression of numerous oncogenic and tumor suppressive microRNAs (miRs). Zeb1 stimulated pro-migratory cytoskeletal processes by down-regulating miR-34a and activated Rho GTPases through Arhgap1, a Cdc42 GTPase activating protein and novel miR-34a target gene. Poor-prognosis human lung adenocarcinomas were highly enriched in a cytoskeletal gene signature activated by miR-34a down-regulation. These findings suggest that Zeb1 regulates a miR network and drives pro-migratory cytoskeletal processes through miR-34a.
ZEB1 drives prometastatic actin cytoskeletal remodeling by downregulating miR-34a expression.
Specimen part
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