Transcriptomic analyses of Kras induced zebrafish liver cancer
ABSTRACT: The kras transgenic line was generated by using a mifepristone-inducible transgenic system in combination with a Cre-loxP system. Most of the induced transgenic fish developed hepatocellular carcinoma at 6 month-post-induction. Transcriptome profiling of Kras tumor sample (6T1 and 6T2) and control samples (6M1 and 6M2) were generated by deep sequencing, using 3' RNA-SAGE on SOLiD system
Previously three oncogene transgenic zebrafish lines with inducible expression of xmrk, kras or Myc in the liver have been generated and these transgenic lines develop oncogene-addicted liver tumors upon chemical induction. In the current study, comparative transcriptomic approaches were used to examine the correlation of the three induced transgenic liver cancers with human liver cancers. RNA profiles from the three zebrafish tumors indicated relatively small overlaps of significantly deregulat ...[more]
Project description:To study the characteristics and mechanisms of Myc-induced zebrafish liver tumor, next-generation sequencing-based SAGE analyses were used to examine the transcriptomes of tumor and control samples. The results indicated that ribosome proteins were overwhelmingly up-regulated in the Myc-induced liver tumors. Cross-species analyses showed that the zebrafish Myc model correlated well with Myc transgenic mouse models for liver cancers. The Myc-induced zebrafish liver tumors also possessed molecular signatures highly similar to human hepatocellular carcinoma (HCC). Thus, our zebrafish model demonstrated the conserved role of Myc in promoting hepatocarcinogenesis in all vertebrate species. Transcriptome profiling of tumor samples (M+D+) and control samples (M-D-, M+D-, M-D+) were generated by deep sequencing, each in duplicates, using 3' RNA-SAGE on the SOLiD system.
Project description:In the present study, we employed the RNA sequencing platform to examine the molecular response of zebrafish liver to arsenic exposure and carry out detailed transcriptomic analyses for further understanding of molecular toxicity. We found that several important biological processes were perturbed by arsenic exposure, including oxidation reduction, translation, iron ion transport, cell redox and homeostasis, as well as related pathways in metabolism and diseases. Furthermore, as there are currently no biomarker genes available for predicting arsenic exposure, we took the advantage of RNA sequencing platform to identify most suitable biomarker genes from top responsive genes to arsenic exposure. We first validated these top responsive genes by RT-qPCR in zebrafish and then in Japanese medaka (Oryzias latipes) at individual fish level for more robustly responsive genes across different fish species. Transcriptome profiling of arsenic-treated sample and control sample were generated by deep sequencing using 3' RNA-SAGE on the SOLiD system.
Project description:Prostate cancer is the most common cancer in men and AR downstream signalings promote prostate cancer cell proliferation. To investigate the AR signaling, we performed RNA sequence analysis in AR positive prostate cancer cell line, LNCaP. In addition, we used hormone-refractory prostate cancer model cells, Bicalutamide-resistant (BicR) to explore the differences of androgen signaling in prostate cancer progression. Short RNA sequence analysis of androgen-regulated miRNAs in two prostate cancer cells
Project description:Prostate cancer is the most common cancer in men and AR downstream signalings promote prostate cancer cell proliferation. To investigate the AR signaling, we performed RNA sequence analysis in AR positive prostate cancer cell line, LNCaP. RNA sequence analysis of androgen-regulated transcripts in prostate cancer cells
Project description:Prostate cancer is the most common cancer in men and androgen receptor (AR) downstream signalings promote prostate cancer cell proliferation. To investigate the AR signaling, we performed directional RNA sequence analysis in AR positive prostate cancer cell line, LNCaP and VCaP. Using Noncode and GENCODE data sets. We identified androgen-regulated long non-coding RNAs (lncRNAs) in prostate cancer cells. Directional RNA sequence analysis of androgen-regulated lncRNAs in prostate cancer cells
Project description:We sequenced mRNAs and mapping the binding of RNA polymerase 2 in collecting duct cells treat with Vasopressin or vehicle. Confluent mpkCCD cell monolayers were maintained in serum-free medium for 24 h prior to treatment with or without 0.1 nM dDAVP in serum-free medium for 24 h. followed RNA polymerase 2 Chip seq.
Project description:Understanding evolutionary mechanisms underlying expansion and reorganization of the human brain represents an important aspect in analyzing the emergence of cognitive abilities typical of our species. Comparative analyses of neuronal phenotypes in closest living relatives (Pan troglodytes; the common chimpanzee) can shed the light into changes in neuronal morphology compared to the last common ancestor (LCA), opening possibilities for analyses of the timing of their appearance, and the role of evolutionary mechanisms favoring a particular type of information processing in humans. Here, we use induced pluripotent stem cell (iPSC) technology to model neural progenitor cell migration and early development of cortical pyramidal neurons in humans and chimpanzees. In addition, we provide morphological characterization of the early stages of neuronal development in human and chimpanzee transplanted cells, and examine the role of developmental mechanisms previously proposed for the evolutionary expansions of the human brain on the early development of pyramidal neurons in the two species. The strategy proposed here lay down the basis for further comparative analysis between human and non-human primates and opens new avenues for understanding cognitive capability and neurological disease susceptibility differences between species. PolyA RNA-Seq profiling of neural progenitor cells (NPCs) and neurons differentiated from human and chimpanzee iPSCs.
Project description:In this manuscript, we have used RNA-Sequencing experiment to obtain and integrate a variety of genomic features in order to identify signaling pathways that are associated to mutant KRAS lung tumors. 8 lung adenocarcinomas with mutant KRAS in lung tumors and 8 lung adenocarcarcinomas without KRAS mutation of which one sample is ran twice for QC purposes.
Project description:Gene expression profiles in the liver of 9-week-old wild type and diabetic db/db mice were measured by high-throughput sequencing to detect the differentially expressed genes Gene expression profiles of 9-week-old wild type and diabetic db/db mice were generated by high-throughput sequencing using Illumina Genome Analyzer
Project description:We investigated microRNA expression in motoneurons by performing small RNA sequencing of fluorescence-activated cell sorting (FACS)-isolated motoneurons labelled with the Hb9:gfp transgenic reporter and Hb9:gfp negative non-motoneurons including spinal interneurons. We find that one microRNA, microRNA-218, is highly enriched and abundantly expressed in motoneurons. Furthermore, we find that miR-218 is transcribed from alternative, motoneuron-specific alternative promoters embedded within the Slit2 and Slit3 genes by performing RNA sequencing of FACS-isolated motoneurons and a dissected embryonic floor plate cells which served as a control. Next, we performed RNA sequencing of FACS-isolated wild type (WT) motoneurons and motoneurons lacking miR-218 expression (218DKO motoneurons), and find that a large set of genes (named 'TARGET218' genes) with predicted miR-218 binding sites are de-repressed in the absence of miR-218 expression. Finally, we examine the expression of TARGET218 genes in other neuronal subpopulations by FACS-isolating V1, V2a, and V3 interneurons expressing Cre-inducible fluorescent reporters and performing RNA sequencing. We find that the TARGET218 network of genes is depleted in wild-type motoneurons versus these interneuron types. Additionally, these genes are expressed at similar levels in 218DKO motoneurons compared with interneuron subtypes, suggesting that this genetic network. Examination of miRNA expression in spinal neuron subpopulations.