DOCSLIB.ORG

Genome-Wide Studies on the Molecular Functions of Pax7 in Adult Muscle Satellite Cells

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Genome-Wide Studies on the Molecular Functions of Pax7 in Adult Muscle Satellite Cells Genome-Wide Studies on the Molecular Functions of Pax7 in Adult Muscle Satellite Cells Vincent Punch Thesis submitted to the Faculty of Graduate and Postdoctoral Studies in partial fulfillment of the requirements for a Ph.D. degree in Cellular and Molecular Medicine Department of Cellular and Molecular Medicine Faculty of Medicine University of Ottawa © Vincent Punch, Ottawa, Canada, 2011 ii Abstract Pax3 and Pax7 belong to a family of conserved transcription factors that play important and diverse roles in development. In the embryo, they carry out similar roles in neural and somite development, but Pax7 fails to compensate for critical functions of Pax3 in the development of limb musculature. Conversely, in the adult, Pax7 is necessary for the maintenance and survival of muscle satellite cells, whereas Pax3 cannot effectively fulfill these roles in the absence of Pax7. To identify the unique roles of Pax7 in adult muscle cells, we have analyzed global binding of Pax3 and Pax7 by ChIP-Seq. Here, we show that despite highly homologous DNA-binding domains, the majority of binding sites are uniquely recognized by Pax7 and are enriched for homeobox motifs. Genes proximal to conserved, unique Pax7 binding sites cluster into specific functional groups which may reflect the unique biological roles of Pax7. Combining Pax7 binding sites with gene expression data, we describe the regulatory networks directed by Pax7 and show that Pax7 binding is associated with positive gene regulation. Moreover, we show Myf5 is a direct target of Pax7 and identify a novel binding site in the satellite cell control region upstream of Myf5. iii Acknowledgements I would like to thank my fellow lab mates for providing an enjoyable atmosphere and constructive and creative environment. You have each contributed to this project in your own way, by stimulating thought provoking discussions, providing technical assistance, or merely social support. I especially thank Dr. Michael Rudnicki for allowing me the opportunity to undertake this research project, for providing scientific guidance and a superb environment in which to carry out this work. I would like to thank Theodore Perkins, Gareth Palidwor, Chris Porter, and Dr. Hang Yin for useful discussions and brainstorming sessions on how to best analyze our vast amount of data. I thank my advisory committee, Dr. Bernard Jasmin, Dr. David Picketts, and Dr. Luc Sabourin, for their guidance along the way. Finally, I thank my parents for their love and support over the years. You encouraged me to keep going when I wanted to give up and helped me every step of the way. iv Contributions of Collaborators and Co-Authors All technical work and preparations of the thesis and manuscripts were carried out by the thesis author except as otherwise specified. Solexa sequencing of ChIP products was carried out in full by the technical staff of Dr. Frank Grosveld at Erasmus University and Medical Center in Rotterdam, Netherlands. Gareth Palidwor and Chris Porter carried out bioinformatics analyses on ChIP-Seq data and provided the corresponding figures used throughout Chapter 2. Dr. Yoichi Kawabe provided RNA samples for the microarray analysis and all baculovirus generated protein used in these studies, in addition to contributing western blot data for Chapter 3. Dr. Vahab Soleimani provided technical assistance with sample preparation for ChIP-Seq experiments. In vivo analyses of the B195APZ BACs were carried out by Dr. Jaime Carvajal of Dr. Peter Rigby’s group at the Division of Gene Function and Regulation at the Institute of Cancer Research in London, UK. The author carried out experiments and provided data for Figures 4b, 4f, 4g, and 4h in Appendix A. v Contents Abstract .................................................................................................................................... ii Acknowledgements ................................................................................................................. iii Contributions of Collaborators and Co-Authors ...................................................................... iv Contents ..................................................................................................................................... v List of Tables .......................................................................................................................... vii List of Figures ....................................................................................................................... viii List of Abbreviations ................................................................................................................ ix Chapter 1 – General Introduction ......................................................................................... 1 1.1. An Overview of Skeletal Muscle ......................................................................... 2 1.2. Stem Cells Regulate the Growth and Regeneration of Muscle ............................ 3 1.3. Molecular Mechanisms of Myogenic Determination .......................................... 4 1.4. Mechanisms of Embryonic Myogenesis .............................................................. 5 1.5. Molecular Networks Regulating Embryonic Myogenesis ................................... 6 1.6. Satellite Cells and Adult Muscle Regeneration ................................................. 12 1.7. Self-Renewal and Commitment of Satellite Cells ............................................. 13 1.8. Extrinsic Signals Regulating Satellite Cell Activation ...................................... 16 1.9. Roles of Pax3 and Pax7 ..................................................................................... 20 1.10. Alternative Splicing of Pax3 and Pax7 .............................................................. 22 1.11. Human Phenotypes of Pax3/7 Mutations ........................................................... 22 1.12. Systems Biology Approaches to Understanding Myogenic Regulatory Networks ............................................................................................................ 23 1.13. Peripheral Networks ........................................................................................... 24 1.14. Rationale and Hypothesis .................................................................................. 25 Chapter 2 – Transcriptional Dominance of Pax7 in Adult Myogenesis is Due to High- Affinity Recognition of Homeodomain Motifs Relative to Pax3 ....................................... 27 Summary ............................................................................................................................. 29 Introduction ......................................................................................................................... 30 Results ................................................................................................................................. 33 Discussion ........................................................................................................................... 56 Experimental Procedures..................................................................................................... 61 Acknowledgements ............................................................................................................. 67 References ........................................................................................................................... 68 Supplementary Information................................................................................................. 84 Chapter 3 – Myf5 is a Direct Target of Pax7 Regulation in Adult Myoblasts ................. 90 Summary ............................................................................................................................. 92 Introduction ......................................................................................................................... 93 Results ................................................................................................................................. 96 Discussion ......................................................................................................................... 109 Experimental Procedures................................................................................................... 114 Acknowledgements ........................................................................................................... 119 vi References ......................................................................................................................... 120 Supplementary Information............................................................................................... 124 Chapter 4 – General Discussion ......................................................................................... 127 4.1. Overview .......................................................................................................... 128 4.2. Future Directions ............................................................................................. 131 4.3. Significance ...................................................................................................... 135 4.4. Biomedical Implications .................................................................................. 137 4.5. Conclusion ....................................................................................................... 138 References ............................................................................................................................
Load more

Recommended publications
  • In Vivo Studies Using the Classical Mouse Diversity Panel
    The Mouse Diversity Panel Predicts Clinical Drug Toxicity Risk Where Classical Models Fail Alison Harrill, Ph.D The Hamner-UNC Institute for Drug Safety Sciences 0 The Importance of Predicting Clinical Adverse Drug Reactions (ADR) Figure: Cath O’Driscoll Nature Publishing 2004 Risk ID PGx Testing 1 People Respond Differently to Drugs Pharmacogenetic Markers Identified by Genome-Wide Association Drug Adverse Drug Risk Allele Reaction (ADR) Abacavir Hypersensitivity HLA-B*5701 Flucloxacillin Hepatotoxicity Allopurinol Cutaneous ADR HLA-B*5801 Carbamazepine Stevens-Johnson HLA-B*1502 Syndrome Augmentin Hepatotoxicity DRB1*1501 Ximelagatran Hepatotoxicity DRB1*0701 Ticlopidine Hepatotoxicity HLA-A*3303 Average preclinical populations and human hepatocytes lack the diversity to detect incidence of adverse events that occur only in 1/10,000 people. Current Rodent Models of Risk Assessment The Challenge “At a time of extraordinary scientific progress, methods have hardly changed in several decades ([FDA] 2004)… Toxicologists face a major challenge in the twenty-first century. They need to embrace the new “omics” techniques and ensure that they are using the most appropriate animals if their discipline is to become a more effective tool in drug development.” -Dr. Michael Festing Quantitative geneticist Toxicol Pathol. 2010;38(5):681-90 Rodent Models as a Strategy for Hazard Characterization and Pharmacogenetics Genetically defined rodent models may provide ability to: 1. Improve preclinical prediction of drugs that carry a human safety risk 2.
    [Show full text]
  • Human Transcription Factor Protein-Protein Interactions in Health and Disease
    HELKA GÖÖS GÖÖS HELKA Recent Publications in this Series 45/2019 Mgbeahuruike Eunice Ego Evaluation of the Medicinal Uses and Antimicrobial Activity of Piper guineense (Schumach & Thonn) 46/2019 Suvi Koskinen AND DISEASE IN HEALTH INTERACTIONS PROTEIN-PROTEIN FACTOR HUMAN TRANSCRIPTION Near-Occlusive Atherosclerotic Carotid Artery Disease: Study with Computed Tomography Angiography 47/2019 Flavia Fontana DISSERTATIONES SCHOLAE DOCTORALIS AD SANITATEM INVESTIGANDAM Biohybrid Cloaked Nanovaccines for Cancer Immunotherapy UNIVERSITATIS HELSINKIENSIS 48/2019 Marie Mennesson Kainate Receptor Auxiliary Subunits Neto1 and Neto2 in Anxiety and Fear-Related Behaviors 49/2019 Zehua Liu Porous Silicon-Based On-Demand Nanohybrids for Biomedical Applications 50/2019 Veer Singh Marwah Strategies to Improve Standardization and Robustness of Toxicogenomics Data Analysis HELKA GÖÖS 51/2019 Iryna Hlushchenko Actin Regulation in Dendritic Spines: From Synaptic Plasticity to Animal Behavior and Human HUMAN TRANSCRIPTION FACTOR PROTEIN-PROTEIN Neurodevelopmental Disorders 52/2019 Heini Liimatta INTERACTIONS IN HEALTH AND DISEASE Efectiveness of Preventive Home Visits among Community-Dwelling Older People 53/2019 Helena Karppinen Older People´s Views Related to Their End of Life: Will-to-Live, Wellbeing and Functioning 54/2019 Jenni Laitila Elucidating Nebulin Expression and Function in Health and Disease 55/2019 Katarzyna Ciuba Regulation of Contractile Actin Structures in Non-Muscle Cells 56/2019 Sami Blom Spatial Characterisation of Prostate Cancer by Multiplex
    [Show full text]
  • Sureselect Community Design Glasgow Cancer Panels
    SureSelect Community Design Glasgow Cancer Panels Biomarkers with proven or emerging utility Genomics is a key element in precision medicine's potential to transform in predicting outcome and/or drug response/resistance - The clinical space oncology. Hybrid capture-based, targeted next-generation sequencing (NGS) represents a particularly promising technology as it enables the focused profiling of each of the many cancer-relevant loci. This approach allows for Ca rapid and cost-effective detection of most cancer-relevant genomic events, nc Cancer Core with the added advantage of FFPE tissue sample compatibility. er The Glasgow Precision Oncology Laboratory (GPOL) is a team of scientists Haem Cancer Plus with internationally recognized expertise in the technology, biology, and clinical utility of cancer genomics. Among their achievements is their detailed curation of genomic data to define the landscape of clinically and biologically significant genomic events in cancer. This includes not only a published literature review (see references 1-3), but also the International Cancer High confidence cancer genes, including those that are not currently clinically Genome Consortium (ICGC) and the Pan-Cancer Analysis of Whole Genomes actionable - The development space (PCAWG) study. Figure 1. Illustration of the GPOL cancer assay suite of panels that are commercially available as part of The GPOL has leveraged these insights to design the hybrid capture-based Agilent's Community Designs. We currently offer the SureSelect Community Design (CD) Cancer Core, Cancer SureSelect cancer NGS panels. With the SureSelect platform, the GPOL team Plus, and Cancer Haem panels. This figure illustrates the has developed a suite of affordable, fit-for-purpose cancer genomic assays relative size and content overlap of each panel.
    [Show full text]
  • The Role of EZH2 in the Induction and Maintenance of Acute Myeloid Leukaemia
    The Role of EZH2 in the Induction and Maintenance of Acute Myeloid Leukaemia Faisal Basheer Downing College University of Cambridge This dissertation is submitted for the degree of Doctor of Philosophy September 2017 Declaration The work presented in this dissertation was carried out under the supervision of Professor Brian Huntly from November 2013 to November 2016 in the Department of Haematology, University of Cambridge. This dissertation is the result of my own work and includes nothing which is the outcome of work done in collaboration except as declared in the Preface and specified in the text. It is not substantially the same as any that I have submitted, or, is being concurrently submitted for a degree or diploma or other qualification at the University of Cambridge or any other University or similar institution except as declared in the Preface and specified in the text. It does not exceed the prescribed word limit set by the Clinical Medicine and Clinical Veterinary Medicine Degree Committee. Faisal Basheer September 2017 i Acknowledgements First and foremost, I would like to thank my supervisor, Professor Brian Huntly, for providing me with the opportunity to work towards this thesis - for his help, encouragement and support over the last four years of my PhD. His dedicated high-level supervision, meticulous attention to detail and excellent direction throughout this time has undoubtedly helped me to maximise my potential in the lab throughout a highly interesting and rewarding project. I would also like to thank all of my colleagues and friends in the Huntly laboratory over the past four years - working together with all of you as a team has been an unforgettable and rewarding experience.
    [Show full text]
  • Mouse Population-Guided Resequencing Reveals That Variants in CD44 Contribute to Acetaminophen-Induced Liver Injury in Humans
    Downloaded from genome.cshlp.org on October 2, 2021 - Published by Cold Spring Harbor Laboratory Press Letter Mouse population-guided resequencing reveals that variants in CD44 contribute to acetaminophen-induced liver injury in humans Alison H. Harrill,1,2,12 Paul B. Watkins,3,12 Stephen Su,6 Pamela K. Ross,2 David E. Harbourt,5 Ioannis M. Stylianou,7 Gary A. Boorman,8 Mark W. Russo,3 Richard S. Sackler,9 Stephen C. Harris,11 Philip C. Smith,5 Raymond Tennant,8 Molly Bogue,7 Kenneth Paigen,7 Christopher Harris,9,10 Tanupriya Contractor,9 Timothy Wiltshire,5 Ivan Rusyn,1,2,14 and David W. Threadgill1,4,13,14,15 1Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina 27599, USA; 2Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina 27599, USA; 3Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina 27599, USA; 4Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA; 5School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA; 6Department of Mouse Genetics, Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA; 7The Jackson Laboratory, Bar Harbor, Maine 04609, USA; 8National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA; 9Verto Institute Research Laboratories, New Brunswick, New Jersey 08903, USA; 10Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA; 11Purdue Pharma L.P., Stamford, Connecticut 06901, USA; 12Hamner-UNC Center for Drug Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709, USA; 13Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695, USA Interindividual variability in response to chemicals and drugs is a common regulatory concern.
    [Show full text]
  • Expanding the Phenotypic Spectrum of PAX6 Mutations: from Congenital Cataracts to Nystagmus
    G C A T T A C G G C A T genes Article Expanding the Phenotypic Spectrum of PAX6 Mutations: From Congenital Cataracts to Nystagmus Maria Nieves-Moreno 1,* , Susana Noval 1 , Jesus Peralta 1, María Palomares-Bralo 2 , Angela del Pozo 3 , Sixto Garcia-Miñaur 4, Fernando Santos-Simarro 4 and Elena Vallespin 5 1 Department of Ophthalmology, Hospital Universitario La Paz, 28046 Madrid, Spain; [email protected] (S.N.); [email protected] (J.P.) 2 Department of Molecular Developmental Disorders, Medical and Molecular Genetics Institue (INGEMM) IdiPaz, CIBERER, Hospital Universitario La Paz, 28046 Madrid, Spain; [email protected] 3 Department of Bioinformatics, Medical and Molecular Genetics Institue (INGEMM) IdiPaz, CIBERER, Hospital Universitario La Paz, 28046 Madrid, Spain; [email protected] 4 Department of Clinical Genetics, Medical and Molecular Genetics Institue (INGEMM) IdiPaz, CIBERER, Hospital Universitario La Paz, 28046 Madrid, Spain; [email protected] (S.G.-M.); [email protected] (F.S.-S.) 5 Department of Molecular Ophthalmology, Medical and Molecular Genetics Institue (INGEMM) IdiPaz, CIBERER, Hospital Universitario La Paz, 28046 Madrid, Spain; [email protected] * Correspondence: [email protected] Abstract: Background: Congenital aniridia is a complex ocular disorder, usually associated with severe visual impairment, generally caused by mutations on the PAX6 gene. The clinical phenotype of PAX6 mutations is highly variable, making the genotype–phenotype correlations difficult to establish. Methods: we describe the phenotype of eight patients from seven unrelated families Citation: Nieves-Moreno, M.; Noval, with confirmed mutations in PAX6, and very different clinical manifestations.
    [Show full text]
  • Spatial Protein Interaction Networks of the Intrinsically Disordered Transcription Factor C(%3$
    Spatial protein interaction networks of the intrinsically disordered transcription factor C(%3$ Dissertation zur Erlangung des akademischen Grades Doctor rerum naturalium (Dr. rer. nat.) im Fach Biologie/Molekularbiologie eingereicht an der Lebenswissenschaftlichen Fakultät der Humboldt-Universität zu Berlin Von Evelyn Ramberger, M.Sc. Präsidentin der Humboldt-Universität zu Berlin Prof. Dr.-Ing.Dr. Sabine Kunst Dekan der Lebenswissenschaftlichen Fakultät der Humboldt-Universität zu Berlin Prof. Dr. Bernhard Grimm Gutachter: 1. Prof. Dr. Achim Leutz 2. Prof. Dr. Matthias Selbach 3. Prof. Dr. Gunnar Dittmar Tag der mündlichen Prüfung: 12.8.2020 For T. Table of Contents Selbstständigkeitserklärung ....................................................................................1 List of Figures ............................................................................................................2 List of Tables ..............................................................................................................3 Abbreviations .............................................................................................................4 Zusammenfassung ....................................................................................................6 Summary ....................................................................................................................7 1. Introduction ............................................................................................................8 1.1. Disordered proteins
    [Show full text]
  • NIH Public Access Author Manuscript Nature
    NIH Public Access Author Manuscript Nature. Author manuscript; available in PMC 2013 September 21. NIH-PA Author Manuscript Published in final edited form as: Nature. 2013 March 21; 495(7441): 370–374. doi:10.1038/nature11925. Nanog-dependent function of Tet1 and Tet2 in establishment of pluripotency Yael Costa1,*, Junjun Ding2,*, Thorold W. Theunissen1,3,*, Francesco Faiola2,*, Timothy A. Hore4, Pavel V. Shliaha5, Miguel Fidalgo2, Arven Saunders2, Moyra Lawrence1,3, Sabine Dietmann1, Satyabrata Das6, Dana N. Levasseur6, Zhe Li7, Mingjiang Xu7, Wolf Reik4,8, José C.R. Silva1,3,#, and Jianlong Wang2,# 1Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK 2Department of Developmental and Regenerative Biology, Black Family Stem Cell Institute, Graduate School of Biological Sciences, Mount Sinai School of Medicine, New York, NY 10029 3 NIH-PA Author Manuscript Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK 4Epigenetics Programme, The Babraham Institute, Cambridge CB22 3AT, UK 5Cambridge Centre for Proteomics, Cambridge Systems Biology Centre, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR UK 6Department of Internal Medicine, and Program in Molecular and Cellular Biology, University of Iowa, Iowa City, Iowa 52242 7Department of Pediatrics, Indiana University, Indianapolis, IN 46202 8Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK Abstract Molecular control of the pluripotent state is thought to reside in a core circuitry of master transcription factors including the homeodomain-containing protein Nanog1–2, which plays an essential role in establishing ground state pluripotency during somatic cell reprogramming3–4. While the genomic occupancy of Nanog has been extensively investigated, comparatively little is NIH-PA Author Manuscript known about Nanog-associated proteins5 and their contribution to the Nanog-mediated reprogramming process.
    [Show full text]
  • Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
    Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase
    [Show full text]
  • A Genome-Wide CRISPR Screen Identifies Regulators of Beta Cell
    bioRxiv preprint doi: https://doi.org/10.1101/2021.05.28.445984; this version posted May 28, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 A genome-wide CRISPR screen identifies regulators of beta cell 2 function involved in type 2 diabetes risk 3 Antje K Grotz1, Elena Navarro-Guerrero2, Romina J Bevacqua3,4, Roberta Baronio2, Soren K 4 Thomsen1, Sameena Nawaz1, Varsha Rajesh4,5, Agata Wesolowska-Andersen6, Seung K Kim3,4, 5 Daniel Ebner2, Anna L Gloyn1,4,5,6,7* 6 1. Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, 7 University of Oxford, Oxford, OX3 7LE, UK. 8 2. Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 9 7FZ, UK. 10 3. Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA, 11 USA. 12 4. Stanford Diabetes Research Centre, Stanford School of Medicine, Stanford University, Stanford, 13 CA, USA 14 5. Department of Pediatrics, Division of Endocrinology, Stanford School of Medicine, Stanford 15 University, Stanford, CA, USA. 16 6. Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, 17 Oxford, OX3 7BN, UK. 18 7. Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, OX3 19 7LE, UK. 20 21 *Correspondence: Anna L. Gloyn, Division of Endocrinology, Department of Pediatrics, Stanford School of 22 Medicine, Stanford University, Stanford, CA, USA.
    [Show full text]
  • Establishment of a Conditionally Immortalized Wilms Tumor Cell Line with a Homozygous WT1 Deletion Within a Heterozygous 11P13 Deletion and UPD Limited to 11P15
    RESEARCH ARTICLE Establishment of a Conditionally Immortalized Wilms Tumor Cell Line with a Homozygous WT1 Deletion within a Heterozygous 11p13 Deletion and UPD Limited to 11p15 Artur Brandt1, Katharina Löhers1, Manfred Beier1, Barbara Leube1, Carmen de Torres2, Jaume Mora2, Parineeta Arora3, Parmjit S. Jat3, Brigitte Royer-Pokora1* a11111 1 Institute of Human Genetics and Anthropology, Heinrich-Heine University, D-40225, Düsseldorf, Germany, 2 Department of Oncology, Hospital Sant Joan de Deu, 08950 Barcelona, Spain, 3 Department of Neurodegenerative Diseases/ MRC Prion Unit, UCL, Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom * [email protected] OPEN ACCESS Abstract Citation: Brandt A, Löhers K, Beier M, Leube B, de Torres C, Mora J, et al. (2016) Establishment of a We describe a stromal predominant Wilms tumor with focal anaplasia and a complex, tumor Conditionally Immortalized Wilms Tumor Cell Line specific chromosome 11 aberration: a homozygous deletion of the entire WT1 gene within a with a Homozygous WT1 Deletion within a Heterozygous 11p13 Deletion and UPD Limited to heterozygous 11p13 deletion and an additional region of uniparental disomy (UPD) limited 11p15. PLoS ONE 11(5): e0155561. doi:10.1371/ to 11p15.5-p15.2 including the IGF2 gene. The tumor carried a heterozygous p.T41A muta- journal.pone.0155561 tion in CTNNB1. Cells established from the tumor carried the same chromosome 11 aberra- Editor: Keith William Brown, University of Bristol, tion, but a different, homozygous p.S45Δ CTNNB1 mutation. Uniparental disomy (UPD) UNITED KINGDOM 3p21.3pter lead to the homozygous CTNNB1 mutation. The tumor cell line was immortal- Received: October 9, 2015 ized using the catalytic subunit of human telomerase (hTERT) in conjunction with a novel Accepted: April 29, 2016 thermolabile mutant (U19dl89-97tsA58) of SV40 large T antigen (LT).
    [Show full text]
  • Application of Microrna Database Mining in Biomarker Discovery and Identification of Therapeutic Targets for Complex Disease
    Article Application of microRNA Database Mining in Biomarker Discovery and Identification of Therapeutic Targets for Complex Disease Jennifer L. Major, Rushita A. Bagchi * and Julie Pires da Silva * Department of Medicine, Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; [email protected] * Correspondence: [email protected] (R.A.B.); [email protected] (J.P.d.S.) Supplementary Tables Methods Protoc. 2021, 4, 5. https://doi.org/10.3390/mps4010005 www.mdpi.com/journal/mps Methods Protoc. 2021, 4, 5. https://doi.org/10.3390/mps4010005 2 of 25 Table 1. List of all hsa-miRs identified by Human microRNA Disease Database (HMDD; v3.2) analysis. hsa-miRs were identified using the term “genetics” and “circulating” as input in HMDD. Targets CAD hsa-miR-1 Targets IR injury hsa-miR-423 Targets Obesity hsa-miR-499 hsa-miR-146a Circulating Obesity Genetics CAD hsa-miR-423 hsa-miR-146a Circulating CAD hsa-miR-149 hsa-miR-499 Circulating IR Injury hsa-miR-146a Circulating Obesity hsa-miR-122 Genetics Stroke Circulating CAD hsa-miR-122 Circulating Stroke hsa-miR-122 Genetics Obesity Circulating Stroke hsa-miR-26b hsa-miR-17 hsa-miR-223 Targets CAD hsa-miR-340 hsa-miR-34a hsa-miR-92a hsa-miR-126 Circulating Obesity Targets IR injury hsa-miR-21 hsa-miR-423 hsa-miR-126 hsa-miR-143 Targets Obesity hsa-miR-21 hsa-miR-223 hsa-miR-34a hsa-miR-17 Targets CAD hsa-miR-223 hsa-miR-92a hsa-miR-126 Targets IR injury hsa-miR-155 hsa-miR-21 Circulating CAD hsa-miR-126 hsa-miR-145 hsa-miR-21 Targets Obesity hsa-mir-223 hsa-mir-499 hsa-mir-574 Targets IR injury hsa-mir-21 Circulating IR injury Targets Obesity hsa-mir-21 Targets CAD hsa-mir-22 hsa-mir-133a Targets IR injury hsa-mir-155 hsa-mir-21 Circulating Stroke hsa-mir-145 hsa-mir-146b Targets Obesity hsa-mir-21 hsa-mir-29b Methods Protoc.
    [Show full text]