DOCSLIB.ORG

Gene Expression in Thyroid Autonomous Adenomas Provides Insight Into Their Physiopathology

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Gene Expression in Thyroid Autonomous Adenomas Provides Insight Into Their Physiopathology Oncogene (2005) 24, 6902–6916 & 2005 Nature Publishing Group All rights reserved 0950-9232/05 $30.00 www.nature.com/onc Gene expression in thyroid autonomous adenomas provides insight into their physiopathology Sandrine Wattel1, Hortensia Mircescu1, David Venet1, Agnes Burniat1, Brigitte Franc2, Sandra Frank1, Guy Andry3, Jacqueline Van Sande1, Pierre Rocmans1, Jacques E Dumont1, Vincent Detours1 and Carine Maenhaut*,1 1Institute of Interdisciplinary Research, School of Medicine, Free University of Brussels, Brussels, Belgium; 2Service d’Anatomie et de Cytologie Pathologiques, Hoˆpital A Pare´ (AP-HP), Universite´ de Versailles, St-Quentin-en-Yvelines, France; 3Department of Surgery, Institut Bordet, 1000 Brussels, Belgium The purpose of this study was to use the microarray Oncogene (2005) 24, 6902–6916. doi:10.1038/sj.onc.1208849; technology to define expression profiles characteristic of published online 18 July 2005 thyroid autonomous adenomas and relate these findings to physiological mechanisms. Experiments were performed Keywords: thyroid; autonomous adenoma; gene expres- on a series of separated adenomas and their normal sion; microarray counterparts on Micromax cDNA microarrays covering 2400 genes (analysis I), and on a pool of adenomatous tissues and their corresponding normal counterparts using microarrays of 18 000 spots (analysis II). Results for Introduction genes present on the two arrays corroborated and several gene regulations previously determined by Northern Autonomous thyroid adenomas are monoclonal encap- blotting or microarrays in similar lesions were confirmed. sulated benign tumors that grow, metabolize iodide, and Five overexpressed and 24underexpressed genes were also secrete thyroid hormones independently of the normal confirmed by real-time RT–PCR in some of the samples thyrotropin (TSH) control, the main proliferative and used for microarray analysis, and in additional tumor functional stimulus of the thyroid gland (Corvilain specimens. Our results show: (1) a change in the cell et al., 2001). They can be either solitary or part of a populations of the tumor, with a marked decrease in multinodular goiter, and grow rather slowly. Their lymphocytes and blood cells and an increase in endothelial frequency is an inverse function of the iodine dietary cells. The latter increase would correspond to the supply, and they are therefore uncommon in the USA or establishment of a close relation between thyrocytes and in Japan, but very common in Europe (Knudsen et al., endothelial cells and is related to increased N-cadherin 2000; Tonacchera et al., 2000; Dremier et al., 2002). expression. It explains the increased blood flow in the Their autonomous secretion of thyroid hormones tumor; (2) a homogeneity of tumor samples correlating decreases TSH secretion by the classical negative feed- with their common physiopathological mechanism: the back exerted on the pituitary thyrotrophs and on TRH constitutive activation of the thyrotropin (TSH)/cAMP secretion. This leads to functional quiescence of the cascade; (3) a low proportion of regulated genes consistent nonaffected tissue. If untreated, in the presence of with the concept of a minimal deviation tumor; (4) a sufficient iodine supply to allow the synthesis and higher expression of genes coding for specific functional secretion of excess thyroid hormones and once they proteins, consistent with the functional hyperactivity of reach a certain size, autonomous adenomas cause the tumors; (5) an increase of phosphodiesterase gene hyperthyroidism (Ermans and Camus, 1972; Corvilain expression which explains the relatively low cyclic AMP et al., 2001). They therefore represent a major medical levels measured in these tumors; (6) an overexpression of problem and account for about half of the cases of antiapoptotic genes and underexpression of proapoptotic hyperthyroidism in Europe (Russo et al., 1995; Bauch, genes compatible with their low apoptosis rate; (7) an 1998; Corvilain et al., 2001). Clinically, they are overexpression of N-cadherin and downregulation of diagnosed by the presence of hot nodules that take up 99m caveolins, which casts doubt about the use of these high amounts of radioiodide or Tc pertechnetate, and expressions as markers for malignancy. are surrounded by poorly radioactive quiescent tissue, and by low TSH serum levels, with normal or elevated thyroid hormone levels. Their histology represents a mixture in various proportions of micro- and macro- *Correspondence: C Maenhaut, IRIBHM, University of Brussels, follicles surrounded by a well-defined capsula. The Campus Erasme, Building C, 808 route de Lennik, B-1070 Brussels, Belgium; E-mail: [email protected] majority have a monoclonal origin (Namba et al., Received 1 March 2005; revised 3 May 2005; accepted 11 May 2005; 1990; Krohn et al., 1998). A very minor proportion may published online 18 July 2005 degenerate into malignant follicular carcinomas, Gene expression in thyroid autonomous adenomas S Wattel et al 6903 whereas a much higher proportion of cold (i.e. non- Adenomas were identified by scintigraphy and in iodide trapping) follicular adenomas do. some cases by a higher in vitro iodide uptake than the TSH exerts most of its effects via a seven-transmem- control quiescent tissue. The analysed tissue RNAs were brane domain receptor positively coupled to adenylate validated for untreated patients by a NIS RNA cyclase, leading to a rise in intracellular cAMP levels expression higher than in control tissues, as evaluated (Dremier et al., 2002). In Europe and Japan, one of the by RT–PCR (see below). For control purposes, one main mechanisms responsible for the hyperfunction and multinodular goiter with no hyperfunctioning adenoma growth of thyroid autonomous adenomas is the (v6) was compared to normal adjacent tissue. For serial constitutive activation of the cAMP-dependent mito- real-time RT–PCR analysis, 10 samples from 10 new genic cascade, through mutations conferring constitu- patients, all of them untreated, were analysed. tive activity of the TSH receptor (50–80%) or an activating mutation of Gsa (8%) (Russo et al., 1995; Analysis of separated samples (analysis I) Van Sande et al., 1995; Fuhrer et al., 1997; Tonacchera et al., 1999; Vanvooren et al., 2002). Similar mutations Reproducibility of the TSA method in gene expression account for hyperfunctioning nodules in multinodular analysis Tyramide signal amplification in microarray goiters (Tonacchera et al., 1999, 2000; Krohn et al., gene expression is a very useful method when limiting 2000). Their phenotype is reproduced in transgenic mice amounts of RNA are available. To assess its reprodu- expressing the constitutive adenosine A2 receptor cibility, we labeled reverse-transcribed total RNA from (Ledent et al., 1992), constitutive Gsa (Michiels et al., the adenomatous tissue with biotin and total RNA from 1994) or the activator of Gsa choleratoxin (Zeiger et al., the control tissue with fluorescein. We performed 1997). Autonomous adenomas are thus a well-defined hybridization with the reverse combination of dyes as example of the results of long-term stimulation by the well (dye swap), and calculated the averages of the physiological TSH receptor/cAMP-dependent cascade intensity ratios obtained with the two opposite dye of human thyroid tissue in vivo (Dumont et al., 1989). As combinations (tumor/control) (Taniguchi et al., 2001; such, they illustrate the concept of minimal deviation Karsten et al., 2002). A high correlation (96%) between tumors: they are constituted of hyperfunctioning thyroid the ratios of the intensity values was obtained for cells whose operation is uncoupled from their normal duplicate spots on the same array. When comparing the physiological control (Van Sande et al., 1988; Weber, same spot on two different slides, correlation ranged 2002). However, data are scarce about specific gene between 70 and 80%. With microarray data generated expression modifications in these tumors and especially by two independent RNA preparations from the same about their physiopathological consequences. tumor sample (a11/v3), a correlation of 73% was Numerous studies in different tumor types have obtained (data not shown). We thus concluded that shown that gene expression profiling of clinical samples tyramide signal amplification is a consistent and by microarray offers unprecedented opportunities to reproducible method, adequate for our analyses. obtain molecular signatures of the state of the tumors. In this study, we have analysed the pattern of gene Gene expression analysis shows high homogeneity between expression in hyperfunctioning autonomous thyroid different autonomous adenomas For each adenoma/ adenomas and validated the relative expression of control paired sample, experiments were duplicated with selected genes by real-time RT–PCR. The data show dye switching, and the averages of the intensity ratios that several physiological and morphological character- (tumor/control) resulting from each dye combination istics of these adenomas can be explained by their were calculated. A total of 14 tumor samples were transcriptional program. analysed (Table 1). We performed unsupervised hier- archical clustering of the samples to analyse the data. As depicted in Figure 1, a set of up- or downregulated genes Results could be identified, with similar expression in the majority of the tumors, suggesting that thyroid adeno- Two types of analyses were performed: an analysis of mas are relatively homogeneous tissues, based on gene gene expression in
Load more

Recommended publications
  • Transcriptomic Analysis of Human Brain Microvascular Endothelial
    www.nature.com/scientificreports OPEN Transcriptomic analysis of human brain microvascular endothelial cells exposed to laminin binding protein (adhesion lipoprotein) and Streptococcus pneumoniae Irene Jiménez‑Munguía1, Zuzana Tomečková1, Evelína Mochnáčová1, Katarína Bhide1, Petra Majerová2 & Mangesh Bhide1,2* Streptococcus pneumoniae invades the CNS and triggers a strong cellular response. To date, signaling events that occur in the human brain microvascular endothelial cells (hBMECs), in response to pneumococci or its surface adhesins are not mapped comprehensively. We evaluated the response of hBMECs to the adhesion lipoprotein (a laminin binding protein—Lbp) or live pneumococci. Lbp is a surface adhesin recently identifed as a potential ligand, which binds to the hBMECs. Transcriptomic analysis was performed by RNA‑seq of three independent biological replicates and validated with qRT‑PCR using 11 genes. In total 350 diferentially expressed genes (DEGs) were identifed after infection with S. pneumoniae, whereas 443 DEGs when challenged with Lbp. Total 231 DEGs were common in both treatments. Integrative functional analysis revealed participation of DEGs in cytokine, chemokine, TNF signaling pathways and phagosome formation. Moreover, Lbp induced cell senescence and breakdown, and remodeling of ECM. This is the frst report which maps complete picture of cell signaling events in the hBMECs triggered against S. pneumoniae and Lbp. The data obtained here could contribute in a better understanding of the invasion of pneumococci across BBB and underscores role of Lbp adhesin in evoking the gene expression in neurovascular unit. Streptococcus pneumoniae (also known as pneumococcus) is a life-threatening pathogen responsible for high morbidity and mortality rates worldwide1. It can cross the blood–brain barrier (BBB) and cause meningitis, commonly known as pneumococcal meningitis, a rare but life-threatening medical emergency.
    [Show full text]
  • The Rise and Fall of the Bovine Corpus Luteum
    University of Nebraska Medical Center DigitalCommons@UNMC Theses & Dissertations Graduate Studies Spring 5-6-2017 The Rise and Fall of the Bovine Corpus Luteum Heather Talbott University of Nebraska Medical Center Follow this and additional works at: https://digitalcommons.unmc.edu/etd Part of the Biochemistry Commons, Molecular Biology Commons, and the Obstetrics and Gynecology Commons Recommended Citation Talbott, Heather, "The Rise and Fall of the Bovine Corpus Luteum" (2017). Theses & Dissertations. 207. https://digitalcommons.unmc.edu/etd/207 This Dissertation is brought to you for free and open access by the Graduate Studies at DigitalCommons@UNMC. It has been accepted for inclusion in Theses & Dissertations by an authorized administrator of DigitalCommons@UNMC. For more information, please contact [email protected]. THE RISE AND FALL OF THE BOVINE CORPUS LUTEUM by Heather Talbott A DISSERTATION Presented to the Faculty of the University of Nebraska Graduate College in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Biochemistry and Molecular Biology Graduate Program Under the Supervision of Professor John S. Davis University of Nebraska Medical Center Omaha, Nebraska May, 2017 Supervisory Committee: Carol A. Casey, Ph.D. Andrea S. Cupp, Ph.D. Parmender P. Mehta, Ph.D. Justin L. Mott, Ph.D. i ACKNOWLEDGEMENTS This dissertation was supported by the Agriculture and Food Research Initiative from the USDA National Institute of Food and Agriculture (NIFA) Pre-doctoral award; University of Nebraska Medical Center Graduate Student Assistantship; University of Nebraska Medical Center Exceptional Incoming Graduate Student Award; the VA Nebraska-Western Iowa Health Care System Department of Veterans Affairs; and The Olson Center for Women’s Health, Department of Obstetrics and Gynecology, Nebraska Medical Center.
    [Show full text]
  • Detection of Interacting Transcription Factors in Human Tissues Using
    Myšičková and Vingron BMC Genomics 2012, 13(Suppl 1):S2 http://www.biomedcentral.com/1471-2164/13/S1/S2 PROCEEDINGS Open Access Detection of interacting transcription factors in human tissues using predicted DNA binding affinity Alena Myšičková*, Martin Vingron From The Tenth Asia Pacific Bioinformatics Conference (APBC 2012) Melbourne, Australia. 17-19 January 2012 Abstract Background: Tissue-specific gene expression is generally regulated by combinatorial interactions among transcription factors (TFs) which bind to the DNA. Despite this known fact, previous discoveries of the mechanism that controls gene expression usually consider only a single TF. Results: We provide a prediction of interacting TFs in 22 human tissues based on their DNA-binding affinity in promoter regions. We analyze all possible pairs of 130 vertebrate TFs from the JASPAR database. First, all human promoter regions are scanned for single TF-DNA binding affinities with TRAP and for each TF a ranked list of all promoters ordered by the binding affinity is created. We then study the similarity of the ranked lists and detect candidates for TF-TF interaction by applying a partial independence test for multiway contingency tables. Our candidates are validated by both known protein-protein interactions (PPIs) and known gene regulation mechanisms in the selected tissue. We find that the known PPIs are significantly enriched in the groups of our predicted TF-TF interactions (2 and 7 times more common than expected by chance). In addition, the predicted interacting TFs for studied tissues (liver, muscle, hematopoietic stem cell) are supported in literature to be active regulators or to be expressed in the corresponding tissue.
    [Show full text]
  • PARD6A (Human) IP-WB Antibody Pair
    PARD6A (Human) IP-WB Antibody Pair Catalog # : H00050855-PW1 規格 : [ 1 Set ] List All Specification Application Image Product This IP-WB antibody pair set comes with one antibody for Immunoprecipitation-Western Blot Description: immunoprecipitation and another to detect the precipitated protein in western blot. Reactivity: Human Quality Control Immunoprecipitation-Western Blot (IP-WB) Testing: Immunoprecipitation of PARD6A transfected lysate using rabbit polyclonal anti-PARD6A and Protein A Magnetic Bead (U0007), and immunoblotted with mouse polyclonal anti-PARD6A. Supplied Antibody pair set content: Product: 1. Antibody pair for IP: rabbit polyclonal anti-PARD6A (300 ul) 2. Antibody pair for WB: mouse polyclonal anti-PARD6A (50 ul) Storage Store reagents of the antibody pair set at -20°C or lower. Please aliquot Instruction: to avoid repeated freeze thaw cycle. Reagents should be returned to - 20°C storage immediately after use. MSDS: Download Applications Immunoprecipitation-Western Blot Protocol Download Gene Information Entrez GeneID: 50855 Gene Name: PARD6A Gene Alias: PAR-6A,PAR6,PAR6C,PAR6alpha,TAX40,TIP-40 Gene par-6 partitioning defective 6 homolog alpha (C. elegans) Description: Omim ID: 607484 Gene Ontology: Hyperlink Page 1 of 2 2016/5/23 Gene Summary: This gene is a member of the PAR6 family and encodes a protein with a PSD95/Discs-large/ZO1 (PDZ) domain and a semi-Cdc42/Rac interactive binding (CRIB) domain. This cell membrane protein is involved in asymmetrical cell division and cell polarization processes as a member of a multi-protein complex. The protein also has a role in the epithelial-to-mesenchymal transition (EMT) that characterizes the invasive phenotype associated with metastatic carcinomas.
    [Show full text]
  • Identifying and Mapping Cell-Type-Specific Chromatin PNAS PLUS Programming of Gene Expression
    Identifying and mapping cell-type-specific chromatin PNAS PLUS programming of gene expression Troels T. Marstranda and John D. Storeya,b,1 aLewis-Sigler Institute for Integrative Genomics, and bDepartment of Molecular Biology, Princeton University, Princeton, NJ 08544 Edited by Wing Hung Wong, Stanford University, Stanford, CA, and approved January 2, 2014 (received for review July 2, 2013) A problem of substantial interest is to systematically map variation Relating DHS to gene-expression levels across multiple cell in chromatin structure to gene-expression regulation across con- types is challenging because the DHS represents a continuous ditions, environments, or differentiated cell types. We developed variable along the genome not bound to any specific region, and and applied a quantitative framework for determining the exis- the relationship between DHS and gene expression is largely tence, strength, and type of relationship between high-resolution uncharacterized. To exploit variation across cell types and test chromatin structure in terms of DNaseI hypersensitivity and genome- for cell-type-specific relationships between DHS and gene expres- wide gene-expression levels in 20 diverse human cell types. We sion, the measurement units must be placed on a common scale, show that ∼25% of genes show cell-type-specific expression ex- the continuous DHS measure associated to each gene in a well- plained by alterations in chromatin structure. We find that distal defined manner, and all measurements considered simultaneously. regions of chromatin structure (e.g., ±200 kb) capture more genes Moreover, the chromatin and gene-expression relationship may with this relationship than local regions (e.g., ±2.5 kb), yet the local only manifest in a single cell type, making standard measures of regions show a more pronounced effect.
    [Show full text]
  • Abl Family Tyrosine Kinases Govern Igg Extravasation in the Skin in a Murine Pemphigus Model
    ARTICLE https://doi.org/10.1038/s41467-019-12232-3 OPEN Abl family tyrosine kinases govern IgG extravasation in the skin in a murine pemphigus model Sachiko Ono1, Gyohei Egawa1, Takashi Nomura1, Akihiko Kitoh1, Teruki Dainichi 1, Atsushi Otsuka1, Saeko Nakajima1, Masayuki Amagai2, Fumi Matsumoto3, Mami Yamamoto 3, Yoshiaki Kubota4, Toshiyuki Takai5, Tetsuya Honda1 & Kenji Kabashima 1,6 1234567890():,; The pathway of homeostatic IgG extravasation is not fully understood, in spite of its importance for the maintenance of host immunity, the management of autoantibody- mediated disorders, and the use of antibody-based biologics. Here we show in a murine model of pemphigus, a prototypic cutaneous autoantibody-mediated disorder, that blood- circulating IgG extravasates into the skin in a time- and dose-dependent manner under homeostatic conditions. This IgG extravasation is unaffected by depletion of Fcγ receptors, but is largely attenuated by specific ablation of dynamin-dependent endocytic vesicle for- mation in blood endothelial cells (BECs). Among dynamin-dependent endocytic vesicles, IgG co-localizes well with caveolae in cultured BECs. An Abl family tyrosine kinase inhibitor imatinib, which reduces caveolae-mediated endocytosis, impairs IgG extravasation in the skin and attenuates the murine pemphigus manifestations. Our study highlights the kinetics of IgG extravasation in vivo, which might be a clue to understand the pathological mechanism of autoantibody-mediated autoimmune disorders. 1 Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan. 2 Department of Dermatology, Keio University Graduate School of Medicine, Tokyo, Japan. 3 Research Unit/Immunology & Inflammation, Sohyaku, Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Yokohama, Japan. 4 Department of Anatomy, Keio University School of Medicine, Tokyo, Japan.
    [Show full text]
  • Chr21 Protein-Protein Interactions: Enrichment in Products Involved in Intellectual Disabilities, Autism and Late Onset Alzheimer Disease
    bioRxiv preprint doi: https://doi.org/10.1101/2019.12.11.872606; this version posted December 12, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Chr21 protein-protein interactions: enrichment in products involved in intellectual disabilities, autism and Late Onset Alzheimer Disease Julia Viard1,2*, Yann Loe-Mie1*, Rachel Daudin1, Malik Khelfaoui1, Christine Plancon2, Anne Boland2, Francisco Tejedor3, Richard L. Huganir4, Eunjoon Kim5, Makoto Kinoshita6, Guofa Liu7, Volker Haucke8, Thomas Moncion9, Eugene Yu10, Valérie Hindie9, Henri Bléhaut11, Clotilde Mircher12, Yann Herault13,14,15,16,17, Jean-François Deleuze2, Jean- Christophe Rain9, Michel Simonneau1, 18, 19, 20** and Aude-Marie Lepagnol- Bestel1** 1 Centre Psychiatrie & Neurosciences, INSERM U894, 75014 Paris, France 2 Laboratoire de génomique fonctionnelle, CNG, CEA, Evry 3 Instituto de Neurociencias CSIC-UMH, Universidad Miguel Hernandez-Campus de San Juan 03550 San Juan (Alicante), Spain 4 Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA 5 Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Daejeon 34141, Republic of Korea 6 Department of Molecular Biology, Division of Biological Science, Nagoya University Graduate School of Science, Furo, Chikusa, Nagoya, Japan 7 Department of Biological Sciences, University of Toledo, Toledo, OH, 43606, USA 8 Leibniz Forschungsinstitut für Molekulare Pharmakologie
    [Show full text]
  • Poised Lineage Specification in Multipotential Hematopoietic Stem
    Cell Stem Cell Short Article Poised Lineage Specification in Multipotential Hematopoietic Stem and Progenitor Cells by the Polycomb Protein Bmi1 Hideyuki Oguro,1,2 Jin Yuan,1,2 Hitoshi Ichikawa,4 Tomokatsu Ikawa,5 Satoshi Yamazaki,3,6 Hiroshi Kawamoto,5 Hiromitsu Nakauchi,3,6 and Atsushi Iwama1,2,* 1Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan 2JST, CREST 3JST, ERATO Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan 4Genetics Division, National Cancer Center Research Institute, Tokyo, 104-0045, Japan 5Laboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, Japan 6Laboratory of Stem Cell Therapy, Center for Experimental Medicine, Institute of Medical Sciences, University of Tokyo, Tokyo 108-8679, Japan *Correspondence: [email protected] DOI 10.1016/j.stem.2010.01.005 SUMMARY Pietersen and van Lohuizen, 2008). They reside in two main complexes, termed Polycomb repressive complex 1 and 2 Polycomb group (PcG) proteins are essential regula- (PRC1 and PRC2). PRC2 and trithorax group (trxG) proteins tors of stem cells. PcG and trithorax group proteins mark developmental regulator gene promoters with bivalent mark developmental regulator gene promoters with domains consisting of overlapping repressive and activating bivalent domains consisting of overlapping repres- histone modifications to keep developmental regulators sive and activating histone modifications to keep ‘‘poised’’ for activation in embryonic stem cells (ESCs) (Bernstein them poised for activation in embryonic stem cells. et al., 2006; Spivakov and Fisher 2007; Mendenhall and Bern- stein, 2008). Likewise, in adult stem cells, developmental regula- Bmi1, a component of PcG complexes, maintains tors that govern lineage specification are supposedly repressed the self-renewal capacity of adult stem cells, but its epigenetically to maintain their multipotency (Pietersen and van role in multipotency remains obscure.
    [Show full text]
  • A Single-Cell Transcriptional Atlas Identifies Extensive Heterogeneity in the Cellular Composition of Tendons
    bioRxiv preprint doi: https://doi.org/10.1101/801266; this version posted October 10, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. A single-cell transcriptional atlas identifies extensive heterogeneity in the cellular composition of tendons Jacob B Swanson1, Andrea J De Micheli2, Nathaniel P Disser1, Leandro M Martinez1, Nicholas R Walker1,3, Benjamin D Cosgrove2, Christopher L Mendias1,3,* 1Hospital for Special Surgery, New York, NY, USA 2Meining School of Biomedical Engineering, Cornell University, Ithaca, NY, USA 3Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY, USA *Corresponding Author Christopher Mendias, PhD Hospital for Special Surgery 535 E 70th St New York, NY 10021 USA +1 212-606-1785 [email protected] Keywords: tenocyte; tendon fibroblast; pericyte; single-cell RNA sequencing bioRxiv preprint doi: https://doi.org/10.1101/801266; this version posted October 10, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Tendon is a dense, hypocellular connective tissue that transmits forces between muscles and bones. Cellular heterogeneity is increasingly recognized as an important factor in the biological basis of tissue homeostasis and disease, but little is known about the diversity of cells that populate tendon. Our objective was to explore the heterogeneity of cells in mouse Achilles tendons using single-cell RNA sequencing. We identified 13 unique cell types in tendons, including 4 previously undescribed populations of fibroblasts.
    [Show full text]
  • Regulation of Cdc42 and Its Effectors in Epithelial Morphogenesis Franck Pichaud1,2,*, Rhian F
    © 2019. Published by The Company of Biologists Ltd | Journal of Cell Science (2019) 132, jcs217869. doi:10.1242/jcs.217869 REVIEW SUBJECT COLLECTION: ADHESION Regulation of Cdc42 and its effectors in epithelial morphogenesis Franck Pichaud1,2,*, Rhian F. Walther1 and Francisca Nunes de Almeida1 ABSTRACT An overview of Cdc42 Cdc42 – a member of the small Rho GTPase family – regulates cell Cdc42 was discovered in yeast and belongs to a large family of small – polarity across organisms from yeast to humans. It is an essential (20 30 kDa) GTP-binding proteins (Adams et al., 1990; Johnson regulator of polarized morphogenesis in epithelial cells, through and Pringle, 1990). It is part of the Ras-homologous Rho subfamily coordination of apical membrane morphogenesis, lumen formation and of GTPases, of which there are 20 members in humans, including junction maturation. In parallel, work in yeast and Caenorhabditis elegans the RhoA and Rac GTPases, (Hall, 2012). Rho, Rac and Cdc42 has provided important clues as to how this molecular switch can homologues are found in all eukaryotes, except for plants, which do generate and regulate polarity through localized activation or inhibition, not have a clear homologue for Cdc42. Together, the function of and cytoskeleton regulation. Recent studies have revealed how Rho GTPases influences most, if not all, cellular processes. important and complex these regulations can be during epithelial In the early 1990s, seminal work from Alan Hall and his morphogenesis. This complexity is mirrored by the fact that Cdc42 can collaborators identified Rho, Rac and Cdc42 as main regulators of exert its function through many effector proteins.
    [Show full text]
  • KLF2 Induced
    UvA-DARE (Digital Academic Repository) The transcription factor KLF2 in vascular biology Boon, R.A. Publication date 2008 Link to publication Citation for published version (APA): Boon, R. A. (2008). The transcription factor KLF2 in vascular biology. 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:23 Sep 2021 Supplementary data: Genes induced by KLF2 Dekker et al. LocusLink Accession Gene Sequence Description Fold p-value ID number symbol change (FDR) 6654 AK022099 SOS1 cDNA FLJ12037 fis, clone HEMBB1001921. 100.00 5.9E-09 56999 AF086069 ADAMTS9 full length insert cDNA clone YZ35C05. 100.00 1.2E-09 6672 AF085934 SP100 full length insert cDNA clone YR57D07. 100.00 6.7E-13 9031 AF132602 BAZ1B Williams Syndrome critical region WS25 mRNA, partial sequence.
    [Show full text]
  • The Title of the Dissertation
    UNIVERSITY OF CALIFORNIA SAN DIEGO Novel network-based integrated analyses of multi-omics data reveal new insights into CD8+ T cell differentiation and mouse embryogenesis A dissertation submitted in partial satisfaction of the requirements for the degree Doctor of Philosophy in Bioinformatics and Systems Biology by Kai Zhang Committee in charge: Professor Wei Wang, Chair Professor Pavel Arkadjevich Pevzner, Co-Chair Professor Vineet Bafna Professor Cornelis Murre Professor Bing Ren 2018 Copyright Kai Zhang, 2018 All rights reserved. The dissertation of Kai Zhang is approved, and it is accept- able in quality and form for publication on microfilm and electronically: Co-Chair Chair University of California San Diego 2018 iii EPIGRAPH The only true wisdom is in knowing you know nothing. —Socrates iv TABLE OF CONTENTS Signature Page ....................................... iii Epigraph ........................................... iv Table of Contents ...................................... v List of Figures ........................................ viii List of Tables ........................................ ix Acknowledgements ..................................... x Vita ............................................. xi Abstract of the Dissertation ................................. xii Chapter 1 General introduction ............................ 1 1.1 The applications of graph theory in bioinformatics ......... 1 1.2 Leveraging graphs to conduct integrated analyses .......... 4 1.3 References .............................. 6 Chapter 2 Systematic
    [Show full text]