Comparative Gene Expression Profiling of Stromal Cell Matrices
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Sorbonne Université́
Sorbonne Université́ École Doctorale ED515 – Complexité́ du vivant INSERM UMRS 933 : Physiopathologie des maladies génétiques d'expression pédiatrique Mécanismes physiopathologiques impliqués dans la différenciation du tractus génital masculin Matthieu Peycelon Thèse de Doctorat de Génétique Humaine Dirigée par Pr. Jean-Pierre Siffroi Présentée et soutenue publiquement le 19 décembre 2019 Devant un jury composé de : Brigitte BENZACKEN PU-PH Université Paris 13 Rapporteur Anne-Françoise SPINOIT Professeur Université de Gand Rapporteur Irène NETCHINE PU-PH Université Paris 6 Examinateur Nicolas KALFA PU-PH Université de Montpellier Examinateur Alaa EL GHONEIMI PU-PH Université Paris 7 Président Jean-Pierre SIFFROI PU-PH Université Paris 6 Directeur de thèse Sorbonne Université́ École Doctorale ED515 – Complexité́ du vivant INSERM UMRS 933 : Physiopathologie des maladies génétiques d'expression pédiatrique Mécanismes physiopathologiques impliqués dans la différenciation du tractus génital masculin Matthieu Peycelon Thèse de Doctorat de Génétique Humaine Dirigée par Pr. Jean-Pierre Siffroi Présentée et soutenue publiquement le 19 décembre 2019 Devant un jury composé de : Brigitte BENZACKEN PU-PH Université Paris 13 Rapporteur Anne-Françoise SPINOIT Professeur Université de Gand Rapporteur Irène NETCHINE PU-PH Université Paris 6 Examinateur Nicolas KALFA PU-PH Université de Montpellier Examinateur Alaa EL GHONEIMI PU-PH Université Paris 7 Président Jean-Pierre SIFFROI PU-PH Université Paris 6 Directeur de thèse Ce travail de thèse a été réalisé́ sous la direction du Professeur Jean-Pierre Siffroi, au sein de l’unité́ mixte de recherche INSERM / Sorbonne Université UMR_S933 dirigée par le Professeur Serge Amselem. Adresse : Département de Génétique Médicale, Hôpital Armand Trousseau ; 26 avenue du Docteur Arnold Netter, 75012, Paris. -
Dickkopf-1 Promotes Hematopoietic Regeneration Via Direct and Niche-Mediated Mechanisms
ARTICLES Dickkopf-1 promotes hematopoietic regeneration via direct and niche-mediated mechanisms Heather A Himburg1,7, Phuong L Doan2,7, Mamle Quarmyne1,3, Xiao Yan1,3, Joshua Sasine1, Liman Zhao1, Grace V Hancock4, Jenny Kan1, Katherine A Pohl1, Evelyn Tran1, Nelson J Chao2, Jeffrey R Harris2 & John P Chute1,5,6 The role of osteolineage cells in regulating hematopoietic stem cell (HSC) regeneration following myelosuppression is not well understood. Here we show that deletion of the pro-apoptotic genes Bak and Bax in osterix (Osx, also known as Sp7 transcription factor 7)-expressing cells in mice promotes HSC regeneration and hematopoietic radioprotection following total body irradiation. These mice showed increased bone marrow (BM) levels of the protein dickkopf-1 (Dkk1), which was produced in Osx-expressing BM cells. Treatment of irradiated HSCs with Dkk1 in vitro increased the recovery of both long-term repopulating HSCs and progenitor cells, and systemic administration of Dkk1 to irradiated mice increased hematopoietic recovery and improved survival. Conversely, inducible deletion of one allele of Dkk1 in Osx-expressing cells in adult mice inhibited the recovery of BM stem and progenitor cells and of complete blood counts following irradiation. Dkk1 promoted hematopoietic regeneration via both direct effects on HSCs, in which treatment with Dkk1 decreased the levels of mitochondrial reactive oxygen species and suppressed senescence, and indirect effects on BM endothelial cells, in which treatment with Dkk1 induced epidermal growth factor (EGF) secretion. Accordingly, blockade of the EGF receptor partially abrogated Dkk1-mediated hematopoietic recovery. These data identify Dkk1 as a regulator of hematopoietic regeneration and demonstrate paracrine cross-talk between BM osteolineage cells and endothelial cells in regulating hematopoietic reconstitution following injury. -
Supporting Online Material
1 2 3 4 5 6 7 Supplementary Information for 8 9 Fractalkine-induced microglial vasoregulation occurs within the retina and is altered early in diabetic 10 retinopathy 11 12 *Samuel A. Mills, *Andrew I. Jobling, *Michael A. Dixon, Bang V. Bui, Kirstan A. Vessey, Joanna A. Phipps, 13 Ursula Greferath, Gene Venables, Vickie H.Y. Wong, Connie H.Y. Wong, Zheng He, Flora Hui, James C. 14 Young, Josh Tonc, Elena Ivanova, Botir T. Sagdullaev, Erica L. Fletcher 15 * Joint first authors 16 17 Corresponding author: 18 Prof. Erica L. Fletcher. Department of Anatomy & Neuroscience. The University of Melbourne, Grattan St, 19 Parkville 3010, Victoria, Australia. 20 Email: [email protected] ; Tel: +61-3-8344-3218; Fax: +61-3-9347-5219 21 22 This PDF file includes: 23 24 Supplementary text 25 Figures S1 to S10 26 Tables S1 to S7 27 Legends for Movies S1 to S2 28 SI References 29 30 Other supplementary materials for this manuscript include the following: 31 32 Movies S1 to S2 33 34 35 36 1 1 Supplementary Information Text 2 Materials and Methods 3 Microglial process movement on retinal vessels 4 Dark agouti rats were anaesthetized, injected intraperitoneally with rhodamine B (Sigma-Aldrich) to label blood 5 vessels and retinal explants established as described in the main text. Retinal microglia were labelled with Iba-1 6 and imaging performed on an inverted confocal microscope (Leica SP5). Baseline images were taken for 10 7 minutes, followed by the addition of PBS (10 minutes) and then either fractalkine or fractalkine + candesartan 8 (10 minutes) using concentrations outlined in the main text. -
Differential Regulation of Proteoglycan 4 Metabolism in Cartilage by IL-1A, IGF-I, and TGF-B1 T
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Osteoarthritis and Cartilage (2008) 16, 90e97 ª 2007 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.joca.2007.05.009 International Cartilage Repair Society Differential regulation of proteoglycan 4 metabolism in cartilage by IL-1a, IGF-I, and TGF-b1 T. A. Schmidt Ph.D., N. S. Gastelum B.S., E. H. Han M.S., G. E. Nugent-Derfus Ph.D., B. L. Schumacher B.S. and R. L. Sah M.D., Sc.D.* Department of Bioengineering and Whitaker Institute of Biomedical Engineering, University of California-San Diego, La Jolla, CA 92093-0412, United States Summary Objectives: To determine (1) if interleukin-1 alpha (IL-1a), insulin like growth factor I (IGF-I), and transforming growth factor-beta 1 (TGF-b1) regulate proteoglycan 4 (PRG4) metabolism in articular cartilage, in terms of chondrocytes expressing PRG4 and PRG4 bound at the articular surface, and (2) if these features of cartilage PRG4 metabolism correlate with its secretion. Methods: Articular cartilage explants were harvested and cultured for 6 days with or without 10% fetal bovine serum (FBS), alone, or with the addition of 10 ng/ml IL-1a, 300 ng/ml IGF-I, or 10 ng/ml TGF-b1. PRG4 expression by chondrocytes in the cartilage disks was assessed by immunohistochemistry (IHC). PRG4 bound to the articular surface of disks was quantified by extraction and enzyme-linked immunosorbent assay (ELISA). PRG4 secreted into culture medium was quantified by ELISA and characterized by Western Blot. -
PRG4) in Modulating Osteoarthritic Synoviocyte Proliferation and Expression of Matrix Degrading Enzymes Ali Alquraini MCPHS University
Chapman University Chapman University Digital Commons Pharmacy Faculty Articles and Research School of Pharmacy 2017 The Autocrine Role of Proteoglycan-4 (PRG4) in Modulating Osteoarthritic Synoviocyte Proliferation and Expression of Matrix Degrading Enzymes Ali Alquraini MCPHS University Maha Jamal MCPHS University Ling Zhang Rhode Island Hospital Tannin Schmidt University of Calgary Gregory D. Jay Rhode Island Hospital FSeoe nelloxtw pa thige fors aaddndition addal aitutionhorsal works at: http://digitalcommons.chapman.edu/pharmacy_articles Part of the Amino Acids, Peptides, and Proteins Commons, Genetic Phenomena Commons, Other Chemicals and Drugs Commons, and the Pharmaceutical Preparations Commons Recommended Citation Alquraini A, Jamal M, Zhang L, Schmidt T, Jay GD, Elsaid KA. The uta ocrine role of proteoglycan-4 (PRG4) in modulating osteoarthritic synoviocyte proliferation and expression of matrix degrading enzymes. Arthritis Research & Therapy. 2017;19:89. doi:10.1186/s13075-017-1301-5. This Article is brought to you for free and open access by the School of Pharmacy at Chapman University Digital Commons. It has been accepted for inclusion in Pharmacy Faculty Articles and Research by an authorized administrator of Chapman University Digital Commons. For more information, please contact [email protected]. The Autocrine Role of Proteoglycan-4 (PRG4) in Modulating Osteoarthritic Synoviocyte Proliferation and Expression of Matrix Degrading Enzymes Comments This article was originally published in Arthritis Research & Therapy, volume 19, in 2017. DOI: 10.1186/ s13075-017-1301-5 Creative Commons License This work is licensed under a Creative Commons Attribution 4.0 License. Copyright The uthora s Authors Ali Alquraini, Maha Jamal, Ling Zhang, Tannin Schmidt, Gregory D. Jay, and Khaled A. -
PDGF-BB Modulates Hematopoiesis and Tumor Angiogenesis by Inducing Erythropoietin Production in Stromal Cells
ARTICLES PDGF-BB modulates hematopoiesis and tumor angiogenesis by inducing erythropoietin production in stromal cells Yuan Xue1, Sharon Lim1, Yunlong Yang1, Zongwei Wang1, Lasse Dahl Ejby Jensen1, Eva-Maria Hedlund1, Patrik Andersson1, Masakiyo Sasahara2, Ola Larsson3, Dagmar Galter4, Renhai Cao1, Kayoko Hosaka1 & Yihai Cao1,5 The platelet-derived growth factor (PDGF) signaling system contributes to tumor angiogenesis and vascular remodeling. Here we show in mouse tumor models that PDGF-BB induces erythropoietin (EPO) mRNA and protein expression by targeting stromal and perivascular cells that express PDGF receptor-b (PDGFR-b). Tumor-derived PDGF-BB promoted tumor growth, angiogenesis and extramedullary hematopoiesis at least in part through modulation of EPO expression. Moreover, adenoviral delivery of PDGF-BB to tumor-free mice increased both EPO production and erythropoiesis, as well as protecting from irradiation-induced anemia. At the molecular level, we show that the PDGF-BB–PDGFR-b signaling system activates the EPO promoter, acting in part through transcriptional regulation by the transcription factor Atf3, possibly through its association with two additional transcription factors, c-Jun and Sp1. Our findings suggest that PDGF-BB–induced EPO promotes tumor growth through two mechanisms: first, paracrine stimulation of tumor angiogenesis by direct induction of endothelial cell proliferation, migration, sprouting and tube formation, and second, endocrine stimulation of extramedullary hematopoiesis leading to increased oxygen perfusion and protection against tumor-associated anemia. Genetic and epigenetic changes in the tumor environment often lead of tumor blood vessels. Such vascular alterations can eventually to elevated amounts of a variety of angiogenic factors that switch on lead to antiangiogenic drug resistance1,14,15. -
Tissue-Specific Transcriptome for Poeciliopsis Prolifica Reveals
INVESTIGATION Tissue-Specific Transcriptome for Poeciliopsis prolifica Reveals Evidence for Genetic Adaptation Related to the Evolution of a Placental Fish Nathaniel K. Jue,*,1 Robert J. Foley,* David N. Reznick,† Rachel J. O’Neill,* and Michael J. O’Neill*,2 *Institute for Systems Genomics and Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269 and †Department of Biology, University of California, Riverside, CA 92521 ABSTRACT The evolution of the placenta is an excellent model to examine the evolutionary processes KEYWORDS underlying adaptive complexity due to the recent, independent derivation of placentation in divergent transcriptome animal lineages. In fishes, the family Poeciliidae offers the opportunity to study placental evolution with positive selection respect to variation in degree of post-fertilization maternal provisioning among closely related sister gene expression species. In this study, we present a detailed examination of a new reference transcriptome sequence for the placenta live-bearing, matrotrophic fish, Poeciliopsis prolifica, from multiple-tissue RNA-seq data. We describe the fish genetic components active in liver, brain, late-stage embryo, and the maternal placental/ovarian complex, as well as associated patterns of positive selection in a suite of orthologous genes found in fishes. Results indicate the expression of many signaling transcripts, “non-coding” sequences and repetitive elements in the maternal placental/ovarian complex. Moreover, patterns of positive selection in protein sequence evolution were found associated with live-bearing fishes, generally, and the placental P. prolifica, specifi- cally, that appear independent of the general live-bearer lifestyle. Much of the observed patterns of gene expression and positive selection are congruent with the evolution of placentation in fish functionally converging with mammalian placental evolution and with the patterns of rapid evolution facilitated by the teleost-specific whole genome duplication event. -
Early Growth Response 1 Regulates Hematopoietic Support and Proliferation in Human Primary Bone Marrow Stromal Cells
Hematopoiesis SUPPLEMENTARY APPENDIX Early growth response 1 regulates hematopoietic support and proliferation in human primary bone marrow stromal cells Hongzhe Li, 1,2 Hooi-Ching Lim, 1,2 Dimitra Zacharaki, 1,2 Xiaojie Xian, 2,3 Keane J.G. Kenswil, 4 Sandro Bräunig, 1,2 Marc H.G.P. Raaijmakers, 4 Niels-Bjarne Woods, 2,3 Jenny Hansson, 1,2 and Stefan Scheding 1,2,5 1Division of Molecular Hematology, Department of Laboratory Medicine, Lund University, Lund, Sweden; 2Lund Stem Cell Center, Depart - ment of Laboratory Medicine, Lund University, Lund, Sweden; 3Division of Molecular Medicine and Gene Therapy, Department of Labora - tory Medicine, Lund University, Lund, Sweden; 4Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands and 5Department of Hematology, Skåne University Hospital Lund, Skåne, Sweden ©2020 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol. 2019.216648 Received: January 14, 2019. Accepted: July 19, 2019. Pre-published: August 1, 2019. Correspondence: STEFAN SCHEDING - [email protected] Li et al.: Supplemental data 1. Supplemental Materials and Methods BM-MNC isolation Bone marrow mononuclear cells (BM-MNC) from BM aspiration samples were isolated by density gradient centrifugation (LSM 1077 Lymphocyte, PAA, Pasching, Austria) either with or without prior incubation with RosetteSep Human Mesenchymal Stem Cell Enrichment Cocktail (STEMCELL Technologies, Vancouver, Canada) for lineage depletion (CD3, CD14, CD19, CD38, CD66b, glycophorin A). BM-MNCs from fetal long bones and adult hip bones were isolated as reported previously 1 by gently crushing bones (femora, tibiae, fibulae, humeri, radii and ulna) in PBS+0.5% FCS subsequent passing of the cell suspension through a 40-µm filter. -
NG2 Proteoglycan in the Diagnosis, Prognosis and Therapy of Gliomas
Mini Review Int J cell Sci & mol biol Volume 2 Issue 2 - April 2017 Copyright © All rights are reserved by Davide Schiffer DOI : 10.19080/IJCSMB.2017.02.555582 NG2 Proteoglycan in the Diagnosis, Prognosis and Therapy of Gliomas Davide Schiffer*, Laura Annovazzi, Enrica Bovio and Marta Mellai Research Center, Policlinico di Monza Foundation, Italy Submission: February 23, 2017; Published: April 27, 2017 *Corresponding author: Davide Schiffer, Research Center, Policlinico di Monza Foundation, Vercelli, Italy, Tel: ; Fax: ; Email: Abstract expressed during development in glia cells committing themselves to a differentiation. It regulates cell proliferation, migration, invasion and neuronalThe review function concerns through the a crosstalk state of artwith of neuronsNG2 proteoglycan by its extracellular from its firstdomain. description It marks to the its oligodendrocyte utilization in glioma precursor therapy. cells, NG2 differentiate protein is into mature oligodendrocytes, and also astrocytes. It is expressed also in pericytes and it is involved in their relationship with that endothelial cells. NG2 distribution in normal central nervous system and in gliomas is discussed, together with its association with Olig2 and PDGFRa. Recently, it became the focus of attention as a therapeutic target. Various attempts have been made using monoclonal antibodies or RNAi, both in animals and in cell lines. Its ablation resulted in the reduction of glioblastoma cell viability. In children gliomas NG2 distribution is different, but children’s brains are very rich in NG2 cells, so that the possibility of a tumor prevention might be hypothesized. Keywords: NG2; Gliomas; Diagnosis; Therapy Introduction It is activated by ligands through focal adhesion kinase(FAK) Glia cells expressing chondroitin sulfate proteoglycan 4 and mitogen-activated protein kinase(MAPK) and it regulates (CSPG4) are called NG2 (neuron-glia antigen 2) cells and occur cell proliferation, migration, invasion and neuronal function in developing as well as in adult brain. -
TET2 Binds the Androgen Receptor and Loss Is Associated with Prostate Cancer
Oncogene (2016), 1–12 © 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved 0950-9232/16 www.nature.com/onc ORIGINAL ARTICLE TET2 binds the androgen receptor and loss is associated with prostate cancer ML Nickerson1,14, S Das2,KMIm3, S Turan1, SI Berndt4,HLi1,5,HLou1,5, SA Brodie4,6, JN Billaud7, T Zhang8, AJ Bouk4,6, D Butcher9, Z Wang4, L Sun10, K Misner1,WTan1,5, A Esnakula11, D Esposito12, WY Huang4, RN Hoover4, MA Tucker4, JR Keller10, J Boland4,6, K Brown8, SK Anderson1, LE Moore4, WB Isaacs13, SJ Chanock4, M Yeager4,6, M Dean1,14 and T Andresson2 Genetic alterations associated with prostate cancer (PCa) may be identified by sequencing metastatic tumour genomes to identify molecular markers at this lethal stage of disease. Previously, we characterized somatic alterations in metastatic tumours in the methylcytosine dioxygenase ten-eleven translocation 2 (TET2), which is altered in 5–15% of myeloid, kidney, colon and PCas. Genome-wide association studies previously identified non-coding risk variants associated with PCa and melanoma. We perform fine-mapping of PCa risk across TET2 using genotypes from the PEGASUS case-control cohort and identify six new risk variants in introns 1 and 2. Oligonucleotides containing two risk variants are bound by the transcription factor octamer-binding protein 1 (Oct1/POU2F1) and TET2 and Oct1 expression are positively correlated in prostate tumours. TET2 is expressed in normal prostate tissue and reduced in a subset of tumours from the Cancer Genome Atlas (TCGA). Small interfering RNA-mediated TET2 knockdown (KD) increases LNCaP cell proliferation, migration and wound healing, verifying loss drives a cancer phenotype. -
Molecular Analysis of the Genetic Heterogeneity Between Primary and Recurrent Glioblastoma
Syracuse University SURFACE Syracuse University Honors Program Capstone Syracuse University Honors Program Capstone Projects Projects Spring 5-1-2009 Molecular Analysis of the Genetic Heterogeneity Between Primary and Recurrent Glioblastoma Anushi Shah Follow this and additional works at: https://surface.syr.edu/honors_capstone Part of the Biology Commons, and the Genetics and Genomics Commons Recommended Citation Shah, Anushi, "Molecular Analysis of the Genetic Heterogeneity Between Primary and Recurrent Glioblastoma" (2009). Syracuse University Honors Program Capstone Projects. 449. https://surface.syr.edu/honors_capstone/449 This Honors Capstone Project is brought to you for free and open access by the Syracuse University Honors Program Capstone Projects at SURFACE. It has been accepted for inclusion in Syracuse University Honors Program Capstone Projects by an authorized administrator of SURFACE. For more information, please contact [email protected]. Molecular Analysis of the Genetic Heterogeneity Between Primary and Recurrent Glioblastoma A Capstone Project Submitted in Partial Fulfillment of the Requirements of the Renée Crown University Honors Program at Syracuse University Anushi Shah Candidate for B.S. Biology & Psychology and B.A. Anthropology Degree and Renée Crown University Honors May 2009 Honors Capstone Project in: __________Biology__________ Capstone Project Advisor: ____________________________ (Dr. Frank Middleton) Honors Reader: ____________________________ (Dr. Shannon Novak) Honors Director: __ __________________________ Samuel Gorovitz Date: _____________ April 21 st , 2009 Abstract Introduction: Glioblastoma multiforme (GBM) is one of the deadliest forms of brain cancer, and affects more than 18,000 new cases each year in the United States alone. The current standard of treatment for GBM includes surgical removal of the tumor, along with radiation and chemotherapy. -
Ep 2812024 B1
(19) TZZ _ Z _T (11) EP 2 812 024 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 39/015 (2006.01) C07K 14/445 (2006.01) 11.04.2018 Bulletin 2018/15 (86) International application number: (21) Application number: 13704077.0 PCT/EP2013/052557 (22) Date of filing: 08.02.2013 (87) International publication number: WO 2013/117705 (15.08.2013 Gazette 2013/33) (54) TARGETING OF CHONDROITIN SULFATE GLYCANS TARGETING VON CHONDROITINSULFATGLYCANEN CIBLAGE DE GLYCANES DE SULFATE DE CHONDROÏTINE (84) Designated Contracting States: • MADELEINE DAHLBÄCK ET AL: "The AL AT BE BG CH CY CZ DE DK EE ES FI FR GB chondroitin sulfate A-binding site of the GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO VAR2CSA protein involves multiple N-terminal PL PT RO RS SE SI SK SM TR domains", JOURNAL OF BIOLOGICAL Designated Extension States: CHEMISTRY, AMERICAN SOCIETY FOR BA ME BIOCHEMISTRY AND MOLECULAR BIOLOGY, INC, BETHESDA, MD, USA, vol. 286, no. 18, 6 May (30) Priority: 09.02.2012 US 201261596931 P 2011 (2011-05-06), pages 15908-15917, XP002669767, ISSN: 1083-351X, DOI: (43) Date of publication of application: 10.1074/JBC.M110.191510 [retrieved on 17.12.2014 Bulletin 2014/51 2011-03-11] cited in the application • SRIVASTAVA A ET AL: "Var2CSA Minimal CSA (73) Proprietor: Var2 Pharmaceuticals ApS Binding Region Is Located within the N-Terminal 2200 Copenhagen N (DK) Region", PLOS ONE, PUBLIC LIBRARY OF SCIENCE, US, vol.