Cellular and Molecular Architecture of the Human Hematopoietic Hierarchy
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Abolhalaj M Et Al, 2018.Pdf
www.nature.com/scientificreports OPEN Profling dendritic cell subsets in head and neck squamous cell tonsillar cancer and benign tonsils Received: 24 November 2017 Milad Abolhalaj1, David Askmyr2,3, Christina Alexandra Sakellariou1, Kristina Lundberg1, Accepted: 19 April 2018 Lennart Greif2,3 & Malin Lindstedt1 Published: xx xx xxxx Dendritic cells (DCs) have a key role in orchestrating immune responses and are considered important targets for immunotherapy against cancer. In order to develop efective cancer vaccines, detailed knowledge of the micromilieu in cancer lesions is warranted. In this study, fow cytometry and human transcriptome arrays were used to characterize subsets of DCs in head and neck squamous cell tonsillar cancer and compare them to their counterparts in benign tonsils to evaluate subset- selective biomarkers associated with tonsillar cancer. We describe, for the frst time, four subsets of DCs in tonsillar cancer: CD123+ plasmacytoid DCs (pDC), CD1c+, CD141+, and CD1c−CD141− myeloid DCs (mDC). An increased frequency of DCs and an elevated mDC/pDC ratio were shown in malignant compared to benign tonsillar tissue. The microarray data demonstrates characteristics specifc for tonsil cancer DC subsets, including expression of immunosuppressive molecules and lower expression levels of genes involved in development of efector immune responses in DCs in malignant tonsillar tissue, compared to their counterparts in benign tonsillar tissue. Finally, we present target candidates selectively expressed by diferent DC subsets in malignant tonsils and confrm expression of CD206/ MRC1 and CD207/Langerin on CD1c+ DCs at protein level. This study descibes DC characteristics in the context of head and neck cancer and add valuable steps towards future DC-based therapies against tonsillar cancer. -
Redox-Mediated Regulation of the Tyrosine Kinase Zap70
Redox-mediated regulation of the tyrosine kinase Zap70 DISSERTATION zur Erlangung des akademischen Grades doctor rerum naturalium (Dr. rer. nat.) genehmigt durch die Fakultät für Naturwissenschaften der Otto-von-Guericke-Universität von M.Sc. Christoph Thurm geb. am 27.06.1988 in Borna Gutachter: apl. Prof. Dr. Luca Simeoni PD Dr. rer. nat. Marcus Lettau eingereicht am: 02.02.2018 verteidigt am: 06.06.2018 Eigenständigkeitserklärung I. Eigenständigkeitserklärung Christoph Thurm Halberstädter Straße 29 39112 Magdeburg Hiermit erkläre ich, dass ich die von mir eingereichte Dissertation zu dem Thema Redox-mediated regulation of the tyrosine kinase Zap70 selbständig verfasst, nicht schon als Dissertation verwendet habe und die benutzten Hilfsmittel und Quellen vollständig angegeben wurden. Weiterhin erkläre ich, dass ich weder diese noch eine andere Arbeit zur Erlangung des akademischen Grades doctor rerum naturalium (Dr. rer. nat.) an anderen Einrichtungen eingereicht habe. Magdeburg, den 02.02.2018 ____________________________________ M.Sc. Christoph Thurm II ACKNOWLEDGEMENTS II. Acknowledgements Firstly, I would like to express my sincere gratitude to my supervisor Prof. Dr. Luca Simeoni. His extraordinary support during my PhD thesis together with his motivation and knowledge enabled me to pursue my dream. I could not have imagined having a better mentor. Furthermore, I would like to thank Prof. Dr. Burkhart Schraven for giving me the opportunity to work in his institute. His support, ideas, and the lively discussions promoted me to develop as a scientist. Special thanks go also to the whole AG Simeoni/Schraven - Ines, Camilla, Matthias, and Andreas - for the help with experiments, the discussions, and the fun we had. This helped to sustain also the longest days. -
Evaluation of Chromatin Accessibility in Prefrontal Cortex of Individuals with Schizophrenia
ARTICLE DOI: 10.1038/s41467-018-05379-y OPEN Evaluation of chromatin accessibility in prefrontal cortex of individuals with schizophrenia Julien Bryois 1, Melanie E. Garrett2, Lingyun Song3, Alexias Safi3, Paola Giusti-Rodriguez 4, Graham D. Johnson 3, Annie W. Shieh13, Alfonso Buil5, John F. Fullard6, Panos Roussos 6,7,8, Pamela Sklar6, Schahram Akbarian 6, Vahram Haroutunian 6,9, Craig A. Stockmeier 10, Gregory A. Wray3,11, Kevin P. White12, Chunyu Liu13, Timothy E. Reddy 3,14, Allison Ashley-Koch2,15, Patrick F. Sullivan 1,4,16 & Gregory E. Crawford 3,17 1234567890():,; Schizophrenia genome-wide association studies have identified >150 regions of the genome associated with disease risk, yet there is little evidence that coding mutations contribute to this disorder. To explore the mechanism of non-coding regulatory elements in schizophrenia, we performed ATAC-seq on adult prefrontal cortex brain samples from 135 individuals with schizophrenia and 137 controls, and identified 118,152 ATAC-seq peaks. These accessible chromatin regions in the brain are highly enriched for schizophrenia SNP heritability. Accessible chromatin regions that overlap evolutionarily conserved regions exhibit an even higher heritability enrichment, indicating that sequence conservation can further refine functional risk variants. We identify few differences in chromatin accessibility between cases and controls, in contrast to thousands of age-related differential accessible chromatin regions. Altogether, we characterize chromatin accessibility in the human prefrontal cortex, the effect of schizophrenia and age on chromatin accessibility, and provide evidence that our dataset will allow for fine mapping of risk variants. 1 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-17177 Stockholm, Sweden. -
Non-Redundant Dual Functions of the ZAP70 Catalytic and Scaffolding
ical C lin as C e Isakov, J Clinic Case Reports 2012, 2:6 f R o l e DOI: 10.4172/2165-7920.1000e113 a p n o r r t u s o J Journal of Clinical Case Reports ISSN: 2165-7920 Editorial Open Access ZAP70-Related SCID: Non-Redundant Dual Functions of the ZAP70 Catalytic and Scaffolding Regions Noah Isakov* The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences and the Cancer Research Center, Ben Gurion University of the Negev, P.O.B. 653, Beer Sheva 84105, Israel Primary Severe Combined Immunodeficiency (SCID) is a form rearrangement of the actin cytoskeleton. These transient intracellular of heritable immunodeficiency, characterized by impaired adaptive signals permit the activation of selected transcription factors that immune responses [1]. It includes a group of genetic disorders promote the proliferation and differentiation of T cells. originated by defects in one of several different genes that are critical Analysis of the phosphorylation sites of ZAP-70 and their impact for T lymphocyte production and/or function and involve defects in B on the function of the molecule demonstrated that phosphorylation lymphocytes as a primary or secondary cause [2]. of Tyr319, Tyr492 and Tyr493 serves to regulate the ZAP70 catalytic The most common type of SCID is linked to the X chromosome activity [23-25]. However, in vivo activation of T cells results in ZAP70 (X-SCID), and therefore affects only males [3,4]. The X-SCID males phosphorylation on additional tyrosine residues [26,27] which may possess mutations in the interleukin-2 (IL-2) receptor gamma chain also function as putative docking sites for SH2-containing proteins. -
Epithelial Barrier and Dendritic Cell Function in the Intestinal Mucosa
UvA-DARE (Digital Academic Repository) Epithelial barrier and dendritic cell function in the intestinal mucosa Verstege, M.I. Publication date 2010 Link to publication Citation for published version (APA): Verstege, M. I. (2010). Epithelial barrier and dendritic cell function in the intestinal mucosa. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:27 Sep 2021 Chapter 5. Single nucleotide polymorphisms in C- type lectin genes, clustered in the IBD2 and IBD6 susceptibility loci, may play a role in the pathogenesis of inflammatory bowel diseases Simone C. Wolfkamp1,2, Marleen I. Verstege1,2, Sander Meisner2, Pieter C. Stokkers1, Anje A. te Velde2 1. Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam 2. Tytgat Institute for Liver and Intestinal Diseases, Academic Medical Centre, Amsterdam Chapter 5 Abstract The balance between microbes and host defence mechanisms at the mucosal frontier plays an important, yet unclarified role in the pathogenesis of inflammatory bowel disease (IBD). -
C-MET) Prolongs the Survival of Chronic Lymphocytic Leukemic Cells Through STAT3 Phosphorylation: a Potential Role of Mesenchymal Cells in the Disease
SUPPLEMENTARY APPENDIX An interaction between hepatocyte growth factor and its receptor (c-MET) prolongs the survival of chronic lymphocytic leukemic cells through STAT3 phosphorylation: a potential role of mesenchymal cells in the disease Paolo Giannoni,1 Silvia Scaglione,2 Rodolfo Quarto,1,3 Roberto Narcisi,3 Manuela Parodi,1 Enrico Balleari,4 Federica Barbieri,5 Alessandra Pattarozzi,5 Tullio Florio,5 Silvano Ferrini,6 †Giorgio Corte,7 and Daniela de Totero7 1Stem Cell Laboratory, Advanced Biotechnology Center, 16132, Genova; 2Dept. of Communication, Computer and System Sciences (D.I.S.T.), University of Genova, 16132, Genova; 3Dept. of Experimental Medicine (Di.Me.S.), University of Genova, Genova; 4Hematological Dept., San Martino Hospital, 16132, Genova; 5Pharmacology Laboratory, Dept. of Oncology, Biology and Genetics (D.O.Bi.G.), University of Genova, 16132, Genova; 6Immunological Therapies Laboratory and 7Gene Transfer Laboratory, National Institute for Cancer Research, 16132, Genova, Italy Citation: Giannoni P, Scaglione S, Quarto R, Narcisi R, Parodi M, Balleari E, Barbieri F, Pattarozzi A, Florio T, Ferrini S, Corte G, and de Totero D. An interaction between hepatocyte growth factor and its receptor (c-MET) prolongs the survival of chronic lymphocytic leukemic cells through STAT3 phosphorylation: a potential role of mesenchymal cells in the disease. Haematologica 2011;96(7):1015- 1023. doi:10.3324/haematol.2010.029736 Online Supplementary Design and Methods ac.uk/microarray-as/ae/) and analyzed in silico with Bioconductor (open source Version 1.2.0; http://www.bioconductor.org/docs/faq/) Immunofluorescence analysis of cell surface antigen for background subtraction and normalization (series acces- expression on chronic lymphocytic leukemia cells sion numbers detailed in Online Supplementary Table S2). -
RT² Profiler PCR Array (96-Well Format and 384-Well [4 X 96] Format)
RT² Profiler PCR Array (96-Well Format and 384-Well [4 x 96] Format) Human Toll-Like Receptor Signaling Pathway Cat. no. 330231 PAHS-018ZA For pathway expression analysis Format For use with the following real-time cyclers RT² Profiler PCR Array, Applied Biosystems® models 5700, 7000, 7300, 7500, Format A 7700, 7900HT, ViiA™ 7 (96-well block); Bio-Rad® models iCycler®, iQ™5, MyiQ™, MyiQ2; Bio-Rad/MJ Research Chromo4™; Eppendorf® Mastercycler® ep realplex models 2, 2s, 4, 4s; Stratagene® models Mx3005P®, Mx3000P®; Takara TP-800 RT² Profiler PCR Array, Applied Biosystems models 7500 (Fast block), 7900HT (Fast Format C block), StepOnePlus™, ViiA 7 (Fast block) RT² Profiler PCR Array, Bio-Rad CFX96™; Bio-Rad/MJ Research models DNA Format D Engine Opticon®, DNA Engine Opticon 2; Stratagene Mx4000® RT² Profiler PCR Array, Applied Biosystems models 7900HT (384-well block), ViiA 7 Format E (384-well block); Bio-Rad CFX384™ RT² Profiler PCR Array, Roche® LightCycler® 480 (96-well block) Format F RT² Profiler PCR Array, Roche LightCycler 480 (384-well block) Format G RT² Profiler PCR Array, Fluidigm® BioMark™ Format H Sample & Assay Technologies Description The Human Toll-Like Receptor (TLR) Signaling Pathway RT² Profiler PCR Array profiles the expression of 84 genes central to TLR-mediated signal transduction and innate immunity. The TLR family of pattern recognition receptors (PRRs) detects a wide range of bacteria, viruses, fungi and parasites via pathogen-associated molecular patterns (PAMPs). Each receptor binds to specific ligands, initiates a tailored innate immune response to the specific class of pathogen, and activates the adaptive immune response. -
K-RAS Gtpase- and B-RAF Kinase–Mediated T-Cell PNAS PLUS Tolerance Defects in Rheumatoid Arthritis
K-RAS GTPase- and B-RAF kinase–mediated T-cell PNAS PLUS tolerance defects in rheumatoid arthritis Karnail Singha,1, Pratima Deshpandeb,1, Guangjin Lib, Mingcan Yub, Sergey Pryshchepa, Mary Cavanaghb, Cornelia M. Weyandb, and Jörg J. Goronzyb,2 aLowance Center for Human Immunology and Rheumatology, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322; and bDepartment of Medicine, Stanford University School of Medicine and Palo Alto Department of Veterans Affairs Health Care System, Palo Alto, CA 94304 Edited by Dennis A. Carson, University of California at San Diego, La Jolla, CA, and approved April 18, 2012 (received for review November 3, 2011) Autoantibodies to common autoantigens and neoantigens, such the signaling cascade after T-cell receptor (TCR) stimulation. as IgG Fc and citrullinated peptides, are immunological hallmarks Based on the substitution conferring increased phosphatase ac- of rheumatoid arthritis (RA). We examined whether a failure in tivity, it was originally considered a gain of function (12). Recent maintaining tolerance is mediated by defects in T-cell receptor findings, however, have shown that the variant is rapidly de- activation threshold settings. RA T cells responded to stimulation graded, causing T-cell hyperresponsiveness (13). The findings with significantly higher ERK phosphorylation (P < 0.001). Gene of disease-associated HLA-DRB1 alleles and PTPN22 poly- expression arrays of ERK pathway members suggested a higher morphisms indicate that T-cell recognition events and TCR expression of KRAS and BRAF, which was confirmed by quantita- threshold calibration are central to RA pathogenesis (13, 14). tive PCR (P = 0.003), Western blot, and flow cytometry (P < 0.01). -
(12) Patent Application Publication (10) Pub. No.: US 2003/0082511 A1 Brown Et Al
US 20030082511A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2003/0082511 A1 Brown et al. (43) Pub. Date: May 1, 2003 (54) IDENTIFICATION OF MODULATORY Publication Classification MOLECULES USING INDUCIBLE PROMOTERS (51) Int. Cl." ............................... C12O 1/00; C12O 1/68 (52) U.S. Cl. ..................................................... 435/4; 435/6 (76) Inventors: Steven J. Brown, San Diego, CA (US); Damien J. Dunnington, San Diego, CA (US); Imran Clark, San Diego, CA (57) ABSTRACT (US) Correspondence Address: Methods for identifying an ion channel modulator, a target David B. Waller & Associates membrane receptor modulator molecule, and other modula 5677 Oberlin Drive tory molecules are disclosed, as well as cells and vectors for Suit 214 use in those methods. A polynucleotide encoding target is San Diego, CA 92121 (US) provided in a cell under control of an inducible promoter, and candidate modulatory molecules are contacted with the (21) Appl. No.: 09/965,201 cell after induction of the promoter to ascertain whether a change in a measurable physiological parameter occurs as a (22) Filed: Sep. 25, 2001 result of the candidate modulatory molecule. Patent Application Publication May 1, 2003 Sheet 1 of 8 US 2003/0082511 A1 KCNC1 cDNA F.G. 1 Patent Application Publication May 1, 2003 Sheet 2 of 8 US 2003/0082511 A1 49 - -9 G C EH H EH N t R M h so as se W M M MP N FIG.2 Patent Application Publication May 1, 2003 Sheet 3 of 8 US 2003/0082511 A1 FG. 3 Patent Application Publication May 1, 2003 Sheet 4 of 8 US 2003/0082511 A1 KCNC1 ITREXCHO KC 150 mM KC 2000000 so 100 mM induced Uninduced Steady state O 100 200 300 400 500 600 700 Time (seconds) FIG. -
Human Lectins, Their Carbohydrate Affinities and Where to Find Them
biomolecules Review Human Lectins, Their Carbohydrate Affinities and Where to Review HumanFind Them Lectins, Their Carbohydrate Affinities and Where to FindCláudia ThemD. Raposo 1,*, André B. Canelas 2 and M. Teresa Barros 1 1, 2 1 Cláudia D. Raposo * , Andr1 é LAQVB. Canelas‐Requimte,and Department M. Teresa of Chemistry, Barros NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829‐516 Caparica, Portugal; [email protected] 12 GlanbiaLAQV-Requimte,‐AgriChemWhey, Department Lisheen of Chemistry, Mine, Killoran, NOVA Moyne, School E41 of ScienceR622 Co. and Tipperary, Technology, Ireland; canelas‐ [email protected] NOVA de Lisboa, 2829-516 Caparica, Portugal; [email protected] 2* Correspondence:Glanbia-AgriChemWhey, [email protected]; Lisheen Mine, Tel.: Killoran, +351‐212948550 Moyne, E41 R622 Tipperary, Ireland; [email protected] * Correspondence: [email protected]; Tel.: +351-212948550 Abstract: Lectins are a class of proteins responsible for several biological roles such as cell‐cell in‐ Abstract:teractions,Lectins signaling are pathways, a class of and proteins several responsible innate immune for several responses biological against roles pathogens. such as Since cell-cell lec‐ interactions,tins are able signalingto bind to pathways, carbohydrates, and several they can innate be a immuneviable target responses for targeted against drug pathogens. delivery Since sys‐ lectinstems. In are fact, able several to bind lectins to carbohydrates, were approved they by canFood be and a viable Drug targetAdministration for targeted for drugthat purpose. delivery systems.Information In fact, about several specific lectins carbohydrate were approved recognition by Food by andlectin Drug receptors Administration was gathered for that herein, purpose. plus Informationthe specific organs about specific where those carbohydrate lectins can recognition be found by within lectin the receptors human was body. -
Exploring the Role of a PYHIN Protein and Involvement of Caspase-8 in the Regulation and Activation of Inflammasomes
University of Massachusetts Medical School eScholarship@UMMS GSBS Dissertations and Theses Graduate School of Biomedical Sciences 2017-09-12 Different Journeys, Same Destination: Exploring the Role of a PYHIN Protein and Involvement of Caspase-8 in the Regulation and Activation of Inflammasomes Sreya Ghosh University of Massachusetts Medical School Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/gsbs_diss Part of the Immunity Commons, Immunology of Infectious Disease Commons, and the Microbiology Commons Repository Citation Ghosh S. (2017). Different Journeys, Same Destination: Exploring the Role of a PYHIN Protein and Involvement of Caspase-8 in the Regulation and Activation of Inflammasomes. GSBS Dissertations and Theses. https://doi.org/10.13028/M2CD6Z. Retrieved from https://escholarship.umassmed.edu/ gsbs_diss/928 Creative Commons License This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in GSBS Dissertations and Theses by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. Different Journeys, Same Destination: Exploring the Role of a PYHIN Protein and Involvement of Caspase-8 in the Regulation and Activation of Inflammasomes A Dissertation Presented By Sreya Ghosh Submitted to the Faculty of the University of Massachusetts Graduate School of Biomedical Sciences, Worcester in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY September 12, 2017 Immunology and Microbiology Program Different Journeys, Same Destination: Exploring the Role of a PYHIN Protein and Involvement of Caspase-8 in the Regulation and Activation of Inflammasomes A Dissertation Presented By Sreya Ghosh The signatures of the Dissertation Defense Committee signify Completion and approval as to style and content of the Dissertation ____________________________________________ Katherine A. -
CLECSF6 Polyclonal Antibody Catalog # AP73990
10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 CLECSF6 Polyclonal Antibody Catalog # AP73990 Specification CLECSF6 Polyclonal Antibody - Product Information Application WB Primary Accession Q9UMR7 Reactivity Human Host Rabbit Clonality Polyclonal CLECSF6 Polyclonal Antibody - Additional Information Gene ID 50856 Other Names C-type lectin domain family 4 member A (C-type lectin DDB27) (C-type lectin superfamily member 6) (Dendritic cell immunoreceptor) (Lectin-like immunoreceptor) Dilution WB~~WB 1:500-2000, ELISA 1:10000-20000 Format Liquid in PBS containing 50% glycerol, 0.5% BSA and 0.02% sodium azide. Storage Conditions -20℃ CLECSF6 Polyclonal Antibody - Protein Information Name CLEC4A (HGNC:13257) Function C-type lectin receptor that binds carbohydrates mannose and fucose but also weakly interacts with N-acetylglucosamine (GlcNAc) in a Ca(2+)-dependent manner (PubMed:<a href="http://www.uniprot.org/c itations/27015765" target="_blank">27015765</a>). Involved in regulating immune reactivity (PubMed:<a href="http://www.uniprot.org/citations/1825 Page 1/4 10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 8799" target="_blank">18258799</a>, PubMed:<a href="http://www.uniprot.org/ci tations/10438934" target="_blank">10438934</a>). Once triggered by antigen, it is internalized by clathrin-dependent endocytosis and delivers its antigenic cargo into the antigen presentation pathway resulting in cross-priming of CD8(+) T cells. This cross-presentation and cross-priming are enhanced by TLR7 and TLR8 agonists with increased expansion of the CD8(+) T cells, high production of IFNG and TNF with reduced levels of IL4, IL5 and IL13 (PubMed:<a href="http://www.uniprot.org/c itations/18258799" target="_blank">18258799</a>, PubMed:<a href="http://www.uniprot.org/ci tations/20530286" target="_blank">20530286</a>).