In order to understand the transcriptional effects of CD44s expression in a cell line that does not express CD44 in its native form we transfected CD44s into HEK cells and measured the transcriptional chances compared to native HEK cells
CD44 Isoform Status Predicts Response to Treatment with Anti-CD44 Antibody in Cancer Patients.
No sample metadata fields
View SamplesAlthough a large set of data is available concerning organogenesis in animal models, information remains scarce on human organogenesis. In this work, we performed temporal mapping of human fetal pancreatic organogenesis using cell surface markers. We demonstrate that in the human fetal pancreas at 7 weeks of development, the glycoprotein 2 (GP2) marks a multipotent cell population that will differentiate either into the acinar, ductal and endocrine lineages. Development towards the acinar lineage is paralleled by a substantial increase in GP2 expression. Conversely, a subset of the multipotent GP2+ population undergoes endocrine differentiation by down-regulating GP2 and CD142 and turning on NEUROG3, an early marker of endocrine differentiation. Endocrine maturation will progress by up-regulating SUSD2 and lowering ECAD levels. Finally, we show that in vitro differentiation of pancreatic endocrine cells derived from human pluripotent stem cells mimics key in vivo events. Our work constitutes a powerful approach to more precisely define intermediate cell population during conversion of multipotent progenitors into the 3 main human pancreatic cell types (acinar, ductal and endocrine) in vivo. As such, the data pave the way to extend our understanding of the origin of mature human pancreatic cell types and how such lineage decisions are regulated.
Reconstructing human pancreatic differentiation by mapping specific cell populations during development.
Specimen part
View SamplesPostnatal day 4 neonatal rat cardiomyocytes transduced with LacZ or flag-tagged, activated YAP1 (S127A) expressing adenovirus
YAP1, the nuclear target of Hippo signaling, stimulates heart growth through cardiomyocyte proliferation but not hypertrophy.
Treatment
View SamplesInhalation of toxic chemicals, including recent e-cigarettes, often cause life-threatening lung injury. Although exposure to polyhexamethylene guanidine (PHMG)-containing humidifier disinfectant (HD) has been identified as a cause of fatal lung injury, the mechanism underlying HD-associated lung injury (HDLI) is unknown. The present study evaluated global changes in gene expression in lung tissues from patients with PHMG-induced HDLI, and compared gene expression changes in PHMG-induced rat lung tissues. Significantly different expressions in lung tissues between patients with HDLI and unaffected controls were observed. Furthermore, several fibrosis-associated overlapping genes (such as MMP2 and COL1A2) shared between humans with HDLI and rats exposed to PHMG were identified. Interactome network analysis predicted different pathways between children and adults with HDLI: the TGFβ/SMAD signaling pathway was central in adults, whereas other pathways, including integrin signaling, were associated with HDLI in children. Further interactome network analysis revealed that Rap1 and CCKR signaling pathways were significantly enriched in HDLI compared with idiopathic pulmonary fibrosis as well as their recapitulation in the lung tissues of rats exposed to PHMG. Our results suggest that MMP2-mediated different mechanisms between children and adults may be associated with PHMG-induced HDLI development, and Rap1 and CCKR pathways appear to be crucial.
Integrative multi-omics approach for mechanism of humidifier disinfectant-associated lung injury.
Age, Specimen part
View SamplesDespite continual efforts to establish pre-operative prognostic model of gastric cancer by using clinical and pathological parameters, a staging system that reliably separates patients with early and advanced gastric cancer into homogeneous groups with respect to prognosis does not exist. With use of microarray and quantitative RT-PCR technologies, we exploited series of experiments in combination with complementary data analyses on tumor specimens from 161 gastric cancer patients. Various statistical analyses were applied to gene expression data to uncover subgroups of gastric cancer, to identify potential biomarkers associated with prognosis, and to construct molecular predictor of risk from identified prognostic biomarkers.Two subgroups of gastric cancer with strong association with prognosis were uncovered. The robustness of prognostic gene expression signature was validated in independent patient cohort with use of support vector machines prediction model. For easy translation of our finding to clinics, we develop scoring system based on expression of six genes that can predict the likelihood of recurrence after curative resection of tumors. In multivariate analysis, our novel risk score was an independent predictor of recurrence (P=0.004) in cohort of 96 patients, and its robustness was validated in two other independent cohorts. We identified novel prognostic subgroups of gastric cancer that are distinctive in gene expression patterns. Six-gene signature and risk score derived from them has been validated for predicting the likelihood of survival at diagnosis.
Gene expression signature-based prognostic risk score in gastric cancer.
No sample metadata fields
View SamplesUnder steady-state conditions, eosinophils are abundantly found in the small intestinal lamina propria, but their physiological function is largely unexplored. We performed a global gene expression analysis to examine which genes are highly expressed by small intestinal eosinophils (CD11b+CD11c(int)MHCII-SiglecF+) compared with dendritic cells (CD11c+MHCII+).
Small intestinal eosinophils regulate Th17 cells by producing IL-1 receptor antagonist.
Age, Specimen part
View SamplesBackground: Causative genes for autosomal dominantly inherited familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC) have been well characterized. There is, however, another 10-15 % early onset colorectal cancer (CRC) whose genetic components are currently unknown. In this study, we used DNA chip technology to systematically search for genes differentially expressed in early onset CRC.
A susceptibility gene set for early onset colorectal cancer that integrates diverse signaling pathways: implication for tumorigenesis.
Sex, Age, Specimen part
View SamplesReconstructed mutants of yeast by inverse metabolic engineering were characterized by fermentation physiology and tools from systems biology.
Recovery of phenotypes obtained by adaptive evolution through inverse metabolic engineering.
Time
View SamplesDrosophila translationally controled tumor protein (dTCTP) is important to repair double stranded DNA breaks in cell nucleus. However, besides damaged DNA loci, dTCTP is also located in interbands region of polytene chromsomes of salivary gland tissues.
Antagonistic roles of Drosophila Tctp and Brahma in chromatin remodelling and stabilizing repeated sequences.
Specimen part
View SamplesAims We aim to use transcriptome analysis to establish on a genome-wide scale the identity and regulatory clusters of genes that specify microgametogenesis from the haploid microspore to mature functional pollen in Arabidopsis. Background Pollen as the haploid male gametophyte plays a vital role in plant fertility and crop production through the ability to deliver the male gametes in fertilisation. Despite the obvious importance for plant fertility and crop production we have a very limited understanding of the regulatory mechanisms that have evolved to specify male gametophyte development and functions and less than 150 genes have been identified that are gametophytically expressed in the anther.The availability of functional genomic resources now provides the opportunity to undertake a comprehensive approach to describing cellular development in terms of the transcriptome. This approach is particularly powerful where the complete transcriptome of a single developing cell can be analysed. The male gametophyte is a uniquely accessible cell type for such studies, enabling RNA analysis from distinct purified cell populations during development.The proposed experiments are designed to support a current application (P19208, Twell) to investigate the gametophytic transcriptome and transcription factor networks. The results obtained will extend our knowledge of the contribution of haploid gene expression to anther development and will be used directly to extend BBSRC funded work (P15086, Wilson) to investigate the role and targets the MALE STERILE 1 gene (MS1). In particular the data will be used in collaboration to extract haploid gene expression from datasets of transcriptome analysis of staged flower buds of wild type (Ler) and ms1. This work will also complement BBSRC funded work on sporogenesis (G13338, Dickinson and Scott) and meiosis (G15941, Franklin and Jones) that are focussed on earlier steps in anther development. Biological material and methods. Isolated microspores and pollen at 4 different developmental stages will be analysed. We will isolate spores from developmentally staged buds of Ler grown under defined growth conditions. Buds from several batches of 100 plants will be rapidly sorted into 4 groups according to developmental age, uninucleate microspores (UM), bicellular pollen (BP) tricellular pollen (TP) and mature pollen. Spores will be released by gentle mechanical tissue disruption and purified by filtration and purification of spores. We are confident that our spore isolation procedures are rigorous since we could not detect even trace expression of highly abundant sporophytic transcripts such RbcS and Cab transcripts in microarray data from pollen RNA.
Transcriptome analysis of haploid male gametophyte development in Arabidopsis.
Specimen part
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