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zebrafish T cells

Marcello Ceci, Claudia Carlantoni, Maria Azzurra Missinato, Davide Bonvissuto, Bruna Di Giacomo, Riccardo Contu, Nicla Romano
Zebrafish could be an interesting translational model to understand and improve the post-infarction trial and possible regeneration in humans. The adult zebrafish is able to regenerate efficiently after resecting nearly 20% of the ventricular apex. This process requires the concert activation of the epicardium and endocardium, as well as trans-differentiation of pre-existing cardiomyocytes that together replace the lost tissue. The molecular mechanisms involved in this activation process are not completely clarified...
2018: Cell Death Discovery
Zacharias Kontarakis, Andrea Rossi, Sophie Ramas, Michael T Dellinger, Didier Y R Stainier
Organ homeostasis relies upon cellular and molecular processes that restore tissue structure and function in a timely fashion. Lymphatic vessels help maintain fluid equilibrium by returning interstitial fluid that evades venous uptake back to the circulation. Despite its important role in tissue homeostasis, cancer metastasis, and close developmental origins with the blood vasculature, the number of molecular players known to control lymphatic system development is relatively low. Here we show, using genetic approaches in zebrafish and mice, that the endothelial specific microRNA mir-126, previously implicated in vascular integrity, regulates lymphatic development...
March 14, 2018: Developmental Biology
Christina H Stuelten, Carole A Parent, Denise J Montell
Metastasis remains the greatest challenge in the clinical management of cancer. Cell motility is a fundamental and ancient cellular behaviour that contributes to metastasis and is conserved in simple organisms. In this Review, we evaluate insights relevant to human cancer that are derived from the study of cell motility in non-mammalian model organisms. Dictyostelium discoideum, Caenorhabditis elegans, Drosophila melanogaster and Danio rerio permit direct observation of cells moving in complex native environments and lend themselves to large-scale genetic and pharmacological screening...
March 16, 2018: Nature Reviews. Cancer
Dhivya Kumar, Rebecca T Thomason, Maya Yankova, Jonathan D Gitlin, Richard E Mains, Betty A Eipper, Stephen M King
The assembly of membranous extensions such as microvilli and cilia in polarized cells is a tightly regulated, yet poorly understood, process. Peptidylglycine α-amidating monooxygenase (PAM), a membrane enzyme essential for the synthesis of amidated bioactive peptides, was recently identified in motile and non-motile (primary) cilia and has an essential role in ciliogenesis in Chlamydomonas, Schmidtea and mouse. In mammalian cells, changes in PAM levels alter secretion and organization of the actin cytoskeleton...
March 14, 2018: Scientific Reports
Ray Hu, Michael P Morley, Jeffrey Brandimarto, Nathan R Tucker, Victoria A Parsons, Sihai D Zhao, Benjamin Meder, Hugo A Katus, Frank Rühle, Monika Stoll, Eric Villard, François Cambien, Honghuang Lin, Nicholas L Smith, Janine F Felix, Ramachandran S Vasan, Pim van der Harst, Christopher Newton-Cheh, Jin Li, Cecilia E Kim, Hakon Hakonarson, Sridhar Hannenhalli, Euan A Ashley, Christine S Moravec, W H Wilson Tang, Marjorie Maillet, Jeffery D Molkentin, Patrick T Ellinor, Kenneth B Margulies, Thomas P Cappola
BACKGROUND: Inhibition of PKC-α (protein kinase C-α) enhances contractility and cardioprotection in animal models, but effects in humans are unknown. Genotypes at rs9912468 strongly associate with PRKCA expression in the left ventricle, enabling genetic approaches to measure effects of reduced PKC-α in human populations. METHODS AND RESULTS: We analyzed the cis expression quantitative trait locus for PRKCA marked by rs9912468 using 313 left ventricular specimens from European Ancestry patients...
March 2018: Circ Genom Precis Med
Juanjuan Zhao, Mathilda T M Mommersteeg
The Slit ligands and their Robo receptors are well-known for their roles during axon guidance in the central nervous system, but are still relatively unknown in the cardiac field. However, data from different animal models suggest a broad involvement of the pathway in many aspects of heart development, from cardiac cell migration and alignment, lumen formation, chamber formation, to the formation of the ventricular septum, semilunar and atrioventricular valves, caval veins and pericardium. Absence of one or more of the genes in the pathway results in defects ranging from bicuspid aortic valves to ventricular septal defects and abnormal venous connections to the heart...
March 10, 2018: Cardiovascular Research
Alison M Earley, Cameron T Dixon, Celia E Shiau
FOXQ1 is a member of the forkhead-box transcription factor family that has important functions in development, cancer, aging, and many cellular processes. The role of FOXQ1 in cancer biology has raised intense interest, yet much remains poorly understood. We investigated the possible function of the two zebrafish orthologs (foxq1a and foxq1b) of human FOXQ1 in innate immune cell development and function. We employed CRISPR-Cas9 targeted mutagenesis to create null mutations of foxq1a and foxq1b in zebrafish...
2018: PloS One
T Porseryd, N Reyhanian Caspillo, K Volkova, L Elabbas, T Källman, P Dinnétz, P-E Olsson, I Porsch-Hällström
17α-Ethinylestradiol (EE2 ) is a ubiquitous aquatic contaminant shown to decrease fish fertility at low concentrations, especially in fish exposed during development. The mechanisms of the decreased fertility are not fully understood. In this study, we perform transcriptome analysis by RNA sequencing of testes from zebrafish with previously reported lowered fertility due to exposure to low concentrations of EE2 during development. Fish were exposed to 1.2 and 1.6 ng/L (measured concentration; nominal concentrations 3 and 10 ng/L) of EE2 from fertilization to 80 days of age, followed by 82 days of remediation in clean water...
March 8, 2018: General and Comparative Endocrinology
Guang-Ping Liu, Li-Xin Xiang, Tong Shao, Ai-Fu Lin, Jian-Zhong Shao
Peroxiredoxin 1 (Prdx1/Prx1), a ubiquitous antioxidant enzyme involved in preventing oxidative damage and maintaining redox homeostasis, is essential for various cellular activities. Extracellular Prdx1 also plays important roles in innate immune responses. However, little is known about the regulatory functions of Prdx1 in adaptive immunity. In the present study, we report the stimulatory role of Prdx1 in the initiation of adaptive humoral immunity in a zebrafish model. Administration of Prdx1 protein to zebrafish significantly induced the expression of TNF-α, IL-1β, and IL-6 by the Toll-like-receptor-4a-mediated NF-κB signaling pathway and enhanced the activation of MHC-II+ antigen-presenting cells, CD4+ T cells, and mIgM+ B cells...
March 5, 2018: Developmental and Comparative Immunology
Maren Mönnich, Louise Borgeskov, Loretta Breslin, Lis Jakobsen, Michaela Rogowski, Canan Doganli, Jacob M Schrøder, Johanne B Mogensen, Louise Blinkenkjær, Lea M Harder, Emma Lundberg, Stefan Geimer, Søren T Christensen, Jens S Andersen, Lars A Larsen, Lotte B Pedersen
The centrosome is the main microtubule-organizing center in animal cells and comprises a mother and daughter centriole surrounded by pericentriolar material. During formation of primary cilia, the mother centriole transforms into a basal body that templates the ciliary axoneme. Ciliogenesis depends on mother centriole-specific distal appendages, whereas the role of subdistal appendages in ciliary function is unclear. Here, we identify CEP128 as a centriole subdistal appendage protein required for regulating ciliary signaling...
March 6, 2018: Cell Reports
Nicole Endlich, Felix Kliewe, Frances Kindt, Katharina Schmidt, Ahmed M Kotb, Nadine Artelt, Maja T Lindenmeyer, Clemens D Cohen, Franziska Döring, Andreas W Kuss, Kerstin Amann, Marcus J Moeller, Nazanin Kabgani, Antje Blumenthal, Karlhans Endlich
Dedifferentiation and loss of podocytes are the major cause of chronic kidney disease. Dach1, a transcription factor that is essential for cell fate, was found in genome-wide association studies to be associated with the glomerular filtration rate. We found that podocytes express high levels of Dach1 in vivo and to a much lower extent in vitro. Parietal epithelial cells (PECs) that are still under debate to be a type of progenitor cell for podocytes expressed Dach1 only at low levels. The transfection of PECs with a plasmid encoding for Dach1 induced the expression of synaptopodin, a podocyte-specific protein, demonstrated by immunocytochemistry and Western blot...
March 2, 2018: Journal of Cellular and Molecular Medicine
Unni Grimholt
BACKGROUND: In sharks, chickens, rats, frogs, medaka and zebrafish there is haplotypic variation in MHC class I and closely linked genes involved in antigen processing, peptide translocation and peptide loading. At least in chicken, such MHCIa haplotypes of MHCIa, TAP2 and Tapasin are shown to influence the repertoire of pathogen epitopes being presented to CD8+ T-cells with subsequent effect on cell-mediated immune responses. RESULTS: Examining MHCI haplotype variation in Atlantic salmon using transcriptome and genome resources we found little evidence for polymorphism in antigen processing genes closely linked to the classical MHCIa genes...
February 23, 2018: BMC Evolutionary Biology
Pengcheng Cai, Xiaoyu Mao, Jieqiong Zhao, Lingfei Luo
Ribosome biogenesis is a significant process in cells. Dysfunction in this process will result in the defects of protein synthesis and consequently cause the development of specific diseases called ribosomopathies. Mutations in ribosome biogenesis protein Rps19, Rpl5, or Rpl11 can lead to hematopoietic defects in human, thus triggering the disease Diamond Blackfan anemia. However, the regulatory mechanisms of ribosome biogenesis in hematopoiesis remain incompletely understood. In this study, we describe a zebrafish mutant cq42, which carries a nonsense mutation in the gene that encodes ribosome biogenesis 2 homolog (Urb2)...
February 19, 2018: Biochemical and Biophysical Research Communications
Ricardo Laranjeiro, T Katherine Tamai, William Letton, Noémie Hamilton, David Whitmore
Studies from a number of model systems have shown that the circadian clock controls expression of key cell cycle checkpoints, thus providing permissive or inhibitory windows in which specific cell cycle events can occur. However, a major question remains: Is the clock actually regulating the cell cycle through such a gating mechanism or, alternatively, is there a coupling process that controls the speed of cell cycle progression? Using our light-responsive zebrafish cell lines, we address this issue directly by synchronizing the cell cycle in culture simply by changing the entraining light-dark (LD) cycle in the incubator without the need for pharmacological intervention...
February 1, 2018: Journal of Biological Rhythms
Silja Burkhard, Vincent van Eif, Laurence Garric, Vincent M Christoffels, Jeroen Bakkers
The rhythmic contraction of the heart is initiated and controlled by an intrinsic pacemaker system. Cardiac contractions commence at very early embryonic stages and coordination remains crucial for survival. The underlying molecular mechanisms of pacemaker cell development and function are still not fully understood. Heart form and function show high evolutionary conservation. Even in simple contractile cardiac tubes in primitive invertebrates, cardiac function is controlled by intrinsic, autonomous pacemaker cells...
April 27, 2017: Journal of Cardiovascular Development and Disease
Carina Lackmann, Martinez Santos, Sandra Rainieri, Alejandro Barranco, Henner Hollert, Petra Spirhanzlova, Mirna Velki, Thomas-Benjamin Seiler
The modes of action of pollutants are diverse, and a common consequences to pollutant exposure is oxidative stress. This phenomenon is caused by an imbalance or disurption in the control of Reactive Oxygen Species (ROS) resulting in an accumulation of free radicals. Oxidative stress may cause damages to the DNA, phospholipids and proteins, and lead to cell death. Due to the possible contribution of oxidative stress to pollutant toxicity, it is valuable to assess its occurrence, role and mechanism. Detection of oxidative stress at low concentrations soon after the onset of exposure can be a sensitive, general marker for contamination...
January 12, 2018: Chemosphere
Jacoba J Louw, Ricardo Nunes Bastos, Xiaowen Chen, Céline Verdood, Anniek Corveleyn, Yaojuan Jia, Jeroen Breckpot, Marc Gewillig, Hilde Peeters, Massimo M Santoro, Francis Barr, Koenraad Devriendt
Congenital or neonatal cardiomyopathies are commonly associated with a poor prognosis and have multiple etiologies. In two siblings, a male and female, we identified an undescribed type of lethal congenital restrictive cardiomyopathy affecting the right ventricle. We hypothesized a novel autosomal recessive condition. To identify the cause, we performed genetic, in vitro and in vivo studies. Genome-wide SNP typing and parametric linkage analysis was done in a recessive model to identify candidate regions. Exome sequencing analysis was done in unaffected and affected siblings...
January 22, 2018: PLoS Genetics
Zhi-Zhi Liu, Zi-Long Wang, Tae-Ik Choi, Wen-Ting Huang, Han-Tsing Wang, Ying-Ying Han, Lou-Yin Zhu, Hyun-Taek Kim, Jung-Hwa Choi, Jin-Soo Lee, Hyung-Goo Kim, Jian Zhao, Yue Chen, Zhuo Lu, Xiao-Li Tian, Bing-Xing Pan, Bao-Ming Li, Cheol-Hee Kim, Hong Xu
CHARGE syndrome is a congenital disorder affecting multiple organs and mainly caused by mutations in CHD7, a gene encoding a chromatin-remodeling protein. Immunodeficiency and reduced T-cells have been noted in CHARGE syndrome. However, the mechanisms underlying T-lymphopenia are largely unexplored. Here, we observed dramatic decrease of T cells in both chd7-knockdown and -knockout zebrafish embryos. Unexpectedly, hematopoietic stem and progenitor cells and, particularly, lymphoid progenitor cells were increased peripherally in nonthymic areas in chd7-deficient embryos, unlikely to contribute to the T cell decrease...
January 15, 2018: American Journal of Pathology
Mari Tenno, Satoshi Kojo, Divine-Fondzenyuy Lawir, Isabell Hess, Katsuyuki Shiroguchi, Takashi Ebihara, Takaho A Endo, Sawako Muroi, Rumi Satoh, Hiroshi Kawamoto, Thomas Boehm, Ichiro Taniuchi
Multipotent hematopoietic progenitors must acquire thymus-homing capacity to initiate T lymphocyte development. Despite its importance, the transcriptional program underlying this process remains elusive. Cbfβ forms transcription factor complexes with Runx proteins, and here we show that Cbfβ2, encoded by an RNA splice variant of the Cbfb gene, is essential for extrathymic differentiation of T cell progenitors. Furthermore, Cbfβ2 endows extrathymic progenitors with thymus-homing capacity by inducing expression of the principal thymus-homing receptor, Ccr9...
January 17, 2018: Journal of Experimental Medicine
Wei Zhong Leong, Shi Hao Tan, Phuong Cao Thi Ngoc, Stella Amanda, Alice Wei Yee Yam, Wei-Siang Liau, Zhiyuan Gong, Lee N Lawton, Daniel G Tenen, Takaomi Sanda
The oncogenic transcription factor TAL1/SCL induces an aberrant transcriptional program in T-cell acute lymphoblastic leukemia (T-ALL) cells. However, the critical factors that are directly activated by TAL1 and contribute to T-ALL pathogenesis are largely unknown. Here, we identified AT-rich interactive domain 5B (ARID5B) as a collaborating oncogenic factor involved in the transcriptional program in T-ALL. ARID5B expression is down-regulated at the double-negative 2-4 stages in normal thymocytes, while it is induced by the TAL1 complex in human T-ALL cells...
January 11, 2018: Genes & Development
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