Evolution of Fibroblasts in the Lung Metastatic Microenvironment
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Analysis of Gene Expression Data for Gene Ontology
ANALYSIS OF GENE EXPRESSION DATA FOR GENE ONTOLOGY BASED PROTEIN FUNCTION PREDICTION A Thesis Presented to The Graduate Faculty of The University of Akron In Partial Fulfillment of the Requirements for the Degree Master of Science Robert Daniel Macholan May 2011 ANALYSIS OF GENE EXPRESSION DATA FOR GENE ONTOLOGY BASED PROTEIN FUNCTION PREDICTION Robert Daniel Macholan Thesis Approved: Accepted: _______________________________ _______________________________ Advisor Department Chair Dr. Zhong-Hui Duan Dr. Chien-Chung Chan _______________________________ _______________________________ Committee Member Dean of the College Dr. Chien-Chung Chan Dr. Chand K. Midha _______________________________ _______________________________ Committee Member Dean of the Graduate School Dr. Yingcai Xiao Dr. George R. Newkome _______________________________ Date ii ABSTRACT A tremendous increase in genomic data has encouraged biologists to turn to bioinformatics in order to assist in its interpretation and processing. One of the present challenges that need to be overcome in order to understand this data more completely is the development of a reliable method to accurately predict the function of a protein from its genomic information. This study focuses on developing an effective algorithm for protein function prediction. The algorithm is based on proteins that have similar expression patterns. The similarity of the expression data is determined using a novel measure, the slope matrix. The slope matrix introduces a normalized method for the comparison of expression levels throughout a proteome. The algorithm is tested using real microarray gene expression data. Their functions are characterized using gene ontology annotations. The results of the case study indicate the protein function prediction algorithm developed is comparable to the prediction algorithms that are based on the annotations of homologous proteins. -
Podoplanin Regulates Mammary Stem Cell Function and Tumorigenesis by Potentiating Wnt/Β-Catenin Signaling Laura Bresson1,2,3, Marisa M
© 2018. Published by The Company of Biologists Ltd | Development (2018) 145, dev160382. doi:10.1242/dev.160382 STEM CELLS AND REGENERATION RESEARCH ARTICLE Podoplanin regulates mammary stem cell function and tumorigenesis by potentiating Wnt/β-catenin signaling Laura Bresson1,2,3, Marisa M. Faraldo1,4, Amandine Di-Cicco1, Miguel Quintanilla5, Marina A. Glukhova1,4 and Marie-Ange Deugnier1,4,* ABSTRACT K5/14), P-cadherin, smooth muscle-specific contractile proteins, Δ Stem cells (SCs) drive mammary development, giving rise postnatally and the transcription factors Np63 (an isoform of Trp63) and Slug/ to an epithelial bilayer composed of luminal and basal myoepithelial Snail2, which are essential for the maintenance of basal cell identity cells. Dysregulation of SCs is thought to be at the origin of certain breast (Yalcin-Ozuysal et al., 2010; Guo et al., 2012). The luminal cell cancers; however, the molecular identity of SCs and the factors layer is characterized by the expression of K8/18. It includes a regulating their function remain poorly defined. We identified the subset of hormone-sensing cells that express estrogen, progesterone transmembrane protein podoplanin (Pdpn) as a specific marker of the and prolactin receptors (ER, PR and PrlR, respectively) and produce basal compartment, including multipotent SCs, and found Pdpn local mediators involved in the paracrine control of basal and localized at the basal-luminal interface. Embryonic deletion of Pdpn luminal cell function (Brisken and Ataca, 2015). targeted to basal cells diminished basal and luminal SC activity and It is established that both mammary lineages, basal and luminal, affected the expression of several Wnt/β-catenin signaling components originate from a common embryonic stem cell (SC) expressing basal in basal cells. -
Human S100A4 (P9ka) Induces the Metastatic Phenotype Upon Benign Tumour Cells
Oncogene (1998) 17, 465 ± 473 1998 Stockton Press All rights reserved 0950 ± 9232/98 $12.00 http://www.stockton-press.co.uk/onc Human S100A4 (p9Ka) induces the metastatic phenotype upon benign tumour cells Bryony H Lloyd, Angela Platt-Higgins, Philip S Rudland and Roger Barraclough School of Biological Sciences, University of Liverpool, PO Box 147, Liverpool, L69 7ZB, UK The rodent S100-related calcium-binding protein, strengthened by the observation that transgenic mice, S100A4 induces metastasis in non-metastatic rat and expressing elevated levels of S100A4 (p9Ka) from 17 mouse benign mammary cells and co-operates with additional, position-independent rat S100A4 trans- benign-tumour-inducing changes in two transgenic mouse genes, fail to show any detectable phenotype (Davies, models, to yield metastatic mammary tumours. Co- 1993). When these mice are mated with transgenic mice transfection of the human gene for S100A4 with containing additional copies of the activated rodent c- pSV2neo into the benign rat mammary cell line, Rama erbB-2 oncogene, neu, under the control of the MMTV 37, yielded cells which expressed a low level of the LTR (Bouchard et al., 1989), ospring inheriting the endogenous S100A4 mRNA, and either high or neu oncogene suer sporadic mammary tumours after undetectable levels of human S100A4 mRNA. The cells 12 ± 14 months of repeated mating. In contrast which expressed a high level of human S100A4 mRNA ospring inheriting both neu and S100A4 transgenes induced metastasis in the benign rat mammary cell line show an elevated incidence of primary tumours, and, in Rama 37 in an in vivo assay, whereas the cells which addition, metastases in the lungs which account for up expressed an undetectable level of human S100A4 did to 24% of the total lung area (Davies et al., 1996). -
Multivariate Analysis Reveals Differentially Expressed Genes
www.nature.com/scientificreports OPEN Multivariate analysis reveals diferentially expressed genes among distinct subtypes of difuse astrocytic gliomas: diagnostic implications Nerea González‑García1,2, Ana Belén Nieto‑Librero1,2, Ana Luisa Vital3, Herminio José Tao4, María González‑Tablas2,5,6, Álvaro Otero2, Purifcación Galindo‑Villardón1,2, Alberto Orfao2,5,6 & María Dolores Tabernero2,5,6,7* Diagnosis and classifcation of gliomas mostly relies on histopathology and a few genetic markers. Here we interrogated microarray gene expression profles (GEP) of 268 difuse astrocytic gliomas—33 difuse astrocytomas (DA), 52 anaplastic astrocytomas (AA) and 183 primary glioblastoma (GBM)—based on multivariate analysis, to identify discriminatory GEP that might support precise histopathological tumor stratifcation, particularly among inconclusive cases with II–III grade diagnosed, which have diferent prognosis and treatment strategies. Microarrays based GEP was analyzed on 155 difuse astrocytic gliomas (discovery cohort) and validated in another 113 tumors (validation set) via sequential univariate analysis (pairwise comparison) for discriminatory gene selection, followed by nonnegative matrix factorization and canonical biplot for identifcation of discriminatory GEP among the distinct histological tumor subtypes. GEP data analysis identifed a set of 27 genes capable of diferentiating among distinct subtypes of gliomas that might support current histological classifcation. DA + AA showed similar molecular profles with only a few discriminatory genes -
Role of RUNX1 in Aberrant Retinal Angiogenesis Jonathan D
Page 1 of 25 Diabetes Identification of RUNX1 as a mediator of aberrant retinal angiogenesis Short Title: Role of RUNX1 in aberrant retinal angiogenesis Jonathan D. Lam,†1 Daniel J. Oh,†1 Lindsay L. Wong,1 Dhanesh Amarnani,1 Cindy Park- Windhol,1 Angie V. Sanchez,1 Jonathan Cardona-Velez,1,2 Declan McGuone,3 Anat O. Stemmer- Rachamimov,3 Dean Eliott,4 Diane R. Bielenberg,5 Tave van Zyl,4 Lishuang Shen,1 Xiaowu Gai,6 Patricia A. D’Amore*,1,7 Leo A. Kim*,1,4 Joseph F. Arboleda-Velasquez*1 Author affiliations: 1Schepens Eye Research Institute/Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, 20 Staniford St., Boston, MA 02114 2Universidad Pontificia Bolivariana, Medellin, Colombia, #68- a, Cq. 1 #68305, Medellín, Antioquia, Colombia 3C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114 4Retina Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, 243 Charles St., Boston, MA 02114 5Vascular Biology Program, Boston Children’s Hospital, Department of Surgery, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115 6Center for Personalized Medicine, Children’s Hospital Los Angeles, Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027, USA 7Department of Pathology, Harvard Medical School, 25 Shattuck St., Boston, MA 02115 Corresponding authors: Joseph F. Arboleda-Velasquez: [email protected] Ph: (617) 912-2517 Leo Kim: [email protected] Ph: (617) 912-2562 Patricia D’Amore: [email protected] Ph: (617) 912-2559 Fax: (617) 912-0128 20 Staniford St. Boston MA, 02114 † These authors contributed equally to this manuscript Word Count: 1905 Tables and Figures: 4 Diabetes Publish Ahead of Print, published online April 11, 2017 Diabetes Page 2 of 25 Abstract Proliferative diabetic retinopathy (PDR) is a common cause of blindness in the developed world’s working adult population, and affects those with type 1 and type 2 diabetes mellitus. -
Absence of S100A4 in the Mouse Lens Induces an Aberrant Retina-Specific Differentiation Program and Cataract
www.nature.com/scientificreports OPEN Absence of S100A4 in the mouse lens induces an aberrant retina‑specifc diferentiation program and cataract Rupalatha Maddala1*, Junyuan Gao2, Richard T. Mathias2, Tylor R. Lewis1, Vadim Y. Arshavsky1,3, Adriana Levine4, Jonathan M. Backer4,5, Anne R. Bresnick4 & Ponugoti V. Rao1,3* S100A4, a member of the S100 family of multifunctional calcium‑binding proteins, participates in several physiological and pathological processes. In this study, we demonstrate that S100A4 expression is robustly induced in diferentiating fber cells of the ocular lens and that S100A4 (−/−) knockout mice develop late‑onset cortical cataracts. Transcriptome profling of lenses from S100A4 (−/−) mice revealed a robust increase in the expression of multiple photoreceptor‑ and Müller glia‑specifc genes, as well as the olfactory sensory neuron‑specifc gene, S100A5. This aberrant transcriptional profle is characterized by corresponding increases in the levels of proteins encoded by the aberrantly upregulated genes. Ingenuity pathway network and curated pathway analyses of diferentially expressed genes in S100A4 (−/−) lenses identifed Crx and Nrl transcription factors as the most signifcant upstream regulators, and revealed that many of the upregulated genes possess promoters containing a high‑density of CpG islands bearing trimethylation marks at histone H3K27 and/or H3K4, respectively. In support of this fnding, we further documented that S100A4 (−/−) knockout lenses have altered levels of trimethylated H3K27 and H3K4. Taken together, -
Transcriptional Control of Lung Alveolar Type 1 Cell Development and Maintenance by NK Homeobox 2-1
Transcriptional control of lung alveolar type 1 cell development and maintenance by NK homeobox 2-1 Danielle R. Littlea,b, Kamryn N. Gerner-Mauroa, Per Flodbyc, Edward D. Crandallc, Zea Borokc, Haruhiko Akiyamad, Shioko Kimurae, Edwin J. Ostrina,f, and Jichao Chena,1 aDepartment of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030; bUniversity of Texas Health Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030; cDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine and Hastings Center for Pulmonary Research, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033; dDepartment of Orthopedics, Kyoto University, Sakyo, 606-8507 Kyoto, Japan; eLaboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and fDepartment of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 Edited by Clifford J. Tabin, Harvard Medical School, Boston, MA, and approved August 30, 2019 (received for review April 18, 2019) The extraordinarily thin alveolar type 1 (AT1) cell constitutes nearly Hippo signaling promotes progenitor differentiation toward the the entire gas exchange surface and allows passive diffusion of AT1 cell fate (12–14). This growing list of AT1 cell regulators oxygen into the blood stream. Despite such an essential role, the highlights both the underlying complexity and the necessity to transcriptional network controlling AT1 cells remains unclear. Using distinguish direct effects on AT1 cells versus those on progenitors, cell-specific knockout mouse models, genomic profiling, and 3D imag- AT2 cells, or tissue morphology, especially in light of the classical Nkx2-1 ing, we found that NK homeobox 2-1 ( )isexpressedinAT1 observation of rapid AT1 cell-like differentiation of cultured cells and is required for the development and maintenance of AT1 AT2 cells (15). -
S100A4 Purified Maxpab Mouse Polyclonal Antibody (B03P)
S100A4 purified MaxPab mouse polyclonal antibody (B03P) Catalog # : H00006275-B03P 規格 : [ 50 ug ] List All Specification Application Image Product Mouse polyclonal antibody raised against a full-length human S100A4 Western Blot (Transfected lysate) Description: protein. Immunogen: S100A4 (NP_002952.1, 1 a.a. ~ 101 a.a) full-length human protein. Sequence: MACPLEKALDVMVSTFHKYSGKEGDKFKLNKSELKELLTRELPSFLGKR TDEAAFQKLMSNLDSNRDNEVDFQEYCVFLSCIAMMCNEFFEGFPDKQ PRKK enlarge Host: Mouse Reactivity: Human Quality Control Antibody reactive against mammalian transfected lysate. Testing: Storage Buffer: In 1x PBS, pH 7.4 Storage Store at -20°C or lower. Aliquot to avoid repeated freezing and thawing. Instruction: MSDS: Download Datasheet: Download Applications Western Blot (Transfected lysate) Western Blot analysis of S100A4 expression in transfected 293T cell line (H00006275-T05) by S100A4 MaxPab polyclonal antibody. Lane 1: S100A4 transfected lysate(11.70 KDa). Lane 2: Non-transfected lysate. Protocol Download Gene Information Entrez GeneID: 6275 Page 1 of 2 2016/5/21 GeneBank NM_002961.2 Accession#: Protein NP_002952.1 Accession#: Gene Name: S100A4 Gene Alias: 18A2,42A,CAPL,FSP1,MTS1,P9KA,PEL98 Gene S100 calcium binding protein A4 Description: Omim ID: 114210 Gene Ontology: Hyperlink Gene Summary: The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein may function in motility, invasion, and tubulin polymerization. -
Inhibits the Migration of Prostate Cancer Through Reducing S100A4, S100A2, and S100P Expression
5429 Original Article Knockdown of ferritin heavy chain (FTH) inhibits the migration of prostate cancer through reducing S100A4, S100A2, and S100P expression Cuixiu Lu1, Huijun Zhao2, Chenshuo Luo3, Ting Lei4, Man Zhang5,6,7^ 1Clinical Laboratory Medicine, Peking University Ninth School of Clinical Medicine, Beijing, China; 2Clinical Laboratory Medicine, Capital Medical University, Beijing, China; 3Clinical Laboratory Medicine, Peking University Ninth School of Clinical Medicine, Beijing, China; 4Beijing Shijitan Hospital, Capital Medical University, Beijing, China; 5Clinical Laboratory Medicine, Peking University Ninth School of Clinical Medicine, Beijing, China; 6Beijing Shijitan Hospital, Capital Medical University, Beijing, China; 7Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, China Contributions: (I) Conception and design: C Lu, C Luo; (II) Administrative support: M Zhang; (III) Provision of study materials or patients: C Lu, T Lei; (IV) Collection and assembly of data: C Lu, H Zhao; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Man Zhang. Clinical Laboratory Medicine, Peking University Ninth School of Clinical Medicine, Beijing 100038, China. Email: [email protected]. Background: Ferritin plays a key role in the development of prostate cancer (PCa). Our earlier studies showed that the knockdown of ferritin heavy chain (FTH) suppressed the migration and invasion of the prostate cancer cell line (PC3). However, the mechanisms behind FTH in the cell migration regulation of PCa have not been thoroughly investigated. Methods: Isobaric tags for relative and absolute quantitation (iTRAQ) proteomics was used to analyze the protein expression in PC3 cells with FTH knockdown by small interfering RNAs and negative control cells. -
Supplementary Figures and Tables
SUPPLEMENTARY DATA Supplementary Figure 1. Isolation and culture of endothelial cells from surgical specimens of FVM. (A) Representative pre-surgical fundus photograph of a right eye exhibiting a FVM encroaching on the optic nerve (dashed line) causing tractional retinal detachment with blot hemorrhages throughout retina (arrow heads). (B) Magnetic beads (arrows) allow for separation and culturing of enriched cell populations from surgical specimens (scale bar = 100 μm). (C) Cultures of isolated cells stained positively for CD31 representing a successfully isolated enriched population (scale bar = 40 μm). ©2017 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db16-1035/-/DC1 SUPPLEMENTARY DATA Supplementary Figure 2. Efficient siRNA knockdown of RUNX1 expression and function demonstrated by qRT-PCR, Western Blot, and scratch assay. (A) RUNX1 siRNA induced a 60% reduction of RUNX1 expression measured by qRT-PCR 48 hrs post-transfection whereas expression of RUNX2 and RUNX3, the two other mammalian RUNX orthologues, showed no significant changes, indicating specificity of our siRNA. Functional inhibition of Runx1 signaling was demonstrated by a 330% increase in insulin-like growth factor binding protein-3 (IGFBP3) RNA expression level, a known target of RUNX1 inhibition. Western blot demonstrated similar reduction in protein levels. (B) siRNA- 2’s effect on RUNX1 was validated by qRT-PCR and western blot, demonstrating a similar reduction in both RNA and protein. Scratch assay demonstrates functional inhibition of RUNX1 by siRNA-2. ns: not significant, * p < 0.05, *** p < 0.001 ©2017 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db16-1035/-/DC1 SUPPLEMENTARY DATA Supplementary Table 1. -
Transcriptomic Profiles of High and Low Antibody Responders to Smallpox
Genes and Immunity (2013) 14, 277–285 & 2013 Macmillan Publishers Limited All rights reserved 1466-4879/13 www.nature.com/gene ORIGINAL ARTICLE Transcriptomic profiles of high and low antibody responders to smallpox vaccine RB Kennedy1,2, AL Oberg1,3, IG Ovsyannikova1,2, IH Haralambieva1,2, D Grill1,3 and GA Poland1,2 Despite its eradication over 30 years ago, smallpox (as well as other orthopox viruses) remains a pathogen of interest both in terms of biodefense and for its use as a vector for vaccines and immunotherapies. Here we describe the application of mRNA-Seq transcriptome profiling to understanding immune responses in smallpox vaccine recipients. Contrary to other studies examining gene expression in virally infected cell lines, we utilized a mixed population of peripheral blood mononuclear cells in order to capture the essential intercellular interactions that occur in vivo, and would otherwise be lost, using single cell lines or isolated primary cell subsets. In this mixed cell population we were able to detect expression of all annotated vaccinia genes. On the host side, a number of genes encoding cytokines, chemokines, complement factors and intracellular signaling molecules were downregulated upon viral infection, whereas genes encoding histone proteins and the interferon response were upregulated. We also identified a small number of genes that exhibited significantly different expression profiles in subjects with robust humoral immunity compared with those with weaker humoral responses. Our results provide evidence that differential gene regulation patterns may be at work in individuals with robust humoral immunity compared with those with weaker humoral immune responses. Genes and Immunity (2013) 14, 277–285; doi:10.1038/gene.2013.14; published online 18 April 2013 Keywords: Next-generation sequencing; mRNA-Seq; vaccinia virus; smallpox vaccine INTRODUCTION these 44 subjects had two samples (uninfected and vaccinia Vaccinia virus (VACV) is the immunologically cross-protective infected). -
Emerging Role of ODC1 in Neurodevelopmental Disorders and Brain Development
G C A T T A C G G C A T genes Article Emerging Role of ODC1 in Neurodevelopmental Disorders and Brain Development Jeremy W. Prokop 1,2,3,*, Caleb P. Bupp 1,4 , Austin Frisch 1, Stephanie M. Bilinovich 1 , Daniel B. Campbell 1,3,5, Daniel Vogt 1,3,5, Chad R. Schultz 1, Katie L. Uhl 1, Elizabeth VanSickle 4, Surender Rajasekaran 1,6,7 and André S. Bachmann 1,* 1 Department of Pediatrics and Human Development, Michigan State University, Grand Rapids, MI 49503, USA; [email protected] (C.P.B.); [email protected] (A.F.); [email protected] (S.M.B.); [email protected] (D.B.C.); [email protected] (D.V.); [email protected] (C.R.S.); [email protected] (K.L.U.); [email protected] (S.R.) 2 Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA 3 Center for Research in Autism, Intellectual, and Other Neurodevelopmental Disabilities, Michigan State University, East Lansing, MI 48824, USA 4 Spectrum Health Medical Genetics, Grand Rapids, MI 49503, USA; [email protected] 5 Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA 6 Pediatric Intensive Care Unit, Helen DeVos Children’s Hospital, Grand Rapids, MI 49503, USA 7 Office of Research, Spectrum Health, Grand Rapids, MI 49503, USA * Correspondence: [email protected] (J.W.P.); [email protected] (A.S.B.) Abstract: Ornithine decarboxylase 1 (ODC1 gene) has been linked through gain-of-function variants Citation: Prokop, J.W.; Bupp, C.P.; to a rare disease featuring developmental delay, alopecia, macrocephaly, and structural brain anoma- Frisch, A.; Bilinovich, S.M.; Campbell, lies.