Development and function of tissues and organs are powered by the activity of mitochondria. In humans, inherited genetic mutations that lead to progressive mitochondrial pathology often manifest during infancy and can lead to death, reflecting the indispensable nature of mitochondrial function and biogenesis. Here, we describe a zebrafish mutant for the gene mia40a, the life-essential homologue of the evolutionarily conserved Mia40 oxidoreductase which drives the biogenesis of cysteine-rich mitochondrial proteins. We report that mia40a mutant animals undergo progressive cellular respiration defects and develop enlarged mitochondria in skeletal muscles before their ultimate at the larval stage. We generated a rich transcriptomic and proteomic resource that allowed us to identify abnormalities in the development of endodermal organs, in particular the liver and pancreas. We identify the acinar cells of the exocrine pancreas to be severely affected by mutations in the MIA pathway. Our data contribute to a better understanding of the molecular, cellular and organismal effects of mitochondrial deficiency, important for the accurate diagnosis and future treatment strategies of these diseases. Overall design: Embryos obtained from an in-cross of heterozygous mia40awaw1/+ siblings were genotyped at 3 dpf. Pools of five mia40+/+ or mia40waw1/waw1 larvae, derived from the same clutch, were collected at indicated time-points for RNA extraction and transcriptomic profiling. Larvae used in 8 dpf experiments were subjected to external feeding from 5dpf before being collected for the analysis at 8dpf.
Loss of the Mia40a oxidoreductase leads to hepato-pancreatic insufficiency in zebrafish.
Specimen part, Subject
View SamplesThe presence of carcinoma in situ (CIS) lesions in the urinary bladder is associated with a high risk of disease progression to a muscle invasive stage. In this study, we used microarray expression profiling to examine the gene expression patterns in superficial transitional cell carcinoma (sTCC) with surrounding CIS (13 patients), without surrounding CIS lesions (15 patients), and in muscle invasive carcinomas (mTCC; 13 patients). Hierarchical cluster analysis separated the sTCC samples according to the presence or absence of CIS in the surrounding urothelium. We identified a few gene clusters that contained genes with similar expression levels in transitional cell carcinoma (TCC) with surrounding CIS and invasive TCC. However, no close relationship between TCC with adjacent CIS and invasive TCC was observed using hierarchical cluster analysis. Expression profiling of a series of biopsies from normal urothelium and urothelium with CIS lesions from the same urinary bladder revealed that the gene expression found in sTCC with surrounding CIS is found also in CIS biopsies as well as in histologically normal samples adjacent to the CIS lesions. Furthermore, we also identified similar gene expression changes in mTCC samples. We used a supervised learning approach to build a 16-gene molecular CIS classifier. The classifier was able to classify sTCC samples according to the presence or absence of surrounding CIS with a high accuracy. This study demonstrates that a CIS gene expression signature is present not only in CIS biopsies but also in sTCC, mTCC, and, remarkably, in histologically normal urothelium from bladders with CIS. Identification of this expression signature could provide guidance for the selection of therapy and follow-up regimen in patients with early stage bladder cancer.
Gene expression in the urinary bladder: a common carcinoma in situ gene expression signature exists disregarding histopathological classification.
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View SamplesProstate cancer is a leading cause of cancer death amongst males. The main clinical dilemma in treating prostate cancer is the high number of indolent cases that confer a significant risk of over diagnosis and over treatment. In this study we have performed a genome expression profiling of tumor tissue specimens from 36 patients with prostate cancer to identify transcripts that delineate aggressive and indolent cancer. We included normal prostate biopsies from 14 patients in our analysis. Unsupervised hierarchical cluster analysis separated the cancer samples into two groups with a significant overrepresentation of tumors from patients with biochemical recurrence in one of the groups (Chi2, p=0.02). The samples were separated by basically three clusters of genes that showed differential expression between the two sample clusters - totaling 371 transcripts. Ingenuity Pathway Analysis revealed that one cluster contained genes associated with invasive properties of the tumor, another genes associated with the cell cycle, and the last cluster genes involved in several biological functions. We successfully validated the transcripts association with recurrence using two publicly available patient datasets totaling 669 patients. Twelve genes were found to be independent predictors of recurrence in multivariate logistical regression analysis.
Expression profiling of prostate cancer tissue delineates genes associated with recurrence after prostatectomy.
Age, Specimen part
View SamplesWe profile the cell line expression of 279 circRNAs, that are highly expressed across 457 bladder cancer patient samples. Additionally, we investigate their cellular location in fractionated cell lines Overall design: 9 bladder cancer cell lines and 3 fractionated bladder cancer cell lines
Circular RNA expression is abundant and correlated to aggressiveness in early-stage bladder cancer.
Specimen part, Cell line, Subject
View SamplesBACKGROUND
Emmprin and survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder cancer.
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View SamplesAtopic dermatitis (AD) is a common inflammatory skin disease with underlying defects in epidermal function and immune responses. The goal of this study was to investigate differences in gene expression in lesional skin from patients with mild extrinsic or intrinsic AD compared to skin from healthy controls and from lesional psoriasis skin. The aim was to identify differentially expressed genes involved in skin barrier formation and inflammation, and to compare our results with those reported for patients with moderate and severe AD.
Distinct molecular signatures of mild extrinsic and intrinsic atopic dermatitis.
Specimen part, Disease
View SamplesThe vertebrate embryo undergoes a series of dramatic morphological changes as the body extends to form the complete anterior-posterior axis during the somite-forming stages. The molecular mechanisms regulating these complex processes are still largely unknown. We show that the Hippo pathway transcriptional coactivators Yap1 and Wwtr1 are specifically localized to the ectoderm and notochord, and play a critical and unexpected role in posterior body extension by regulating the assembly of Fibronectin underneath the ectoderm and surrounding the notochord. We also find that Yap1/Wwtr1, also acting through Fibronectin, have an essential role in the ectodermal morphogenesis necessary to form the initial dorsal and ventral fins, a process that had been thought to involve bending of an epithelial sheet, but which we now show involves active cell migration. Our results reveal how the Hippo pathway transcriptional program, localized to two specific tissues, acts to control essential morphological events in the vertebrate embryo. Overall design: two biological replicates of tails of yap1/wwtr1 double homozygous mutants and siblings (24 each at 16-18 somite stage) were collected for RNAseq. Tails are tissues of the posterior end until the third newest somite (S-III).
Regulation of posterior body and epidermal morphogenesis in zebrafish by localized Yap1 and Wwtr1.
Specimen part, Subject
View SamplesThe goal of this study is to determine gene expression changes in the adult zebrafish spinal cord at 2 weeks after complete transection. Overall design: 2 samples were analyzed in duplicates: sham injured spinal cord and transected spinal cord at 2 weeks post-injury
Injury-induced ctgfa directs glial bridging and spinal cord regeneration in zebrafish.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
miR-126 regulates angiogenic signaling and vascular integrity.
No sample metadata fields
View SamplesFish, JE, Santoro, MM, Morton, SU, Yu, S, Yeh, RF, Wythe, JD, Ivey, KI, Bruneau, BG, Stainier, DYR, and Srivastava, D. (2008). miR-126 Regulates Angiogenic Signaling and Vascular Integrity. Developmental Cell 15, 272-284.
miR-126 regulates angiogenic signaling and vascular integrity.
No sample metadata fields
View Samples