Table S1 the Four Gene Sets Derived from Gene Expression Profiles of Escs and Differentiated Cells
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Down-Regulation of Stem Cell Genes, Including Those in a 200-Kb Gene Cluster at 12P13.31, Is Associated with in Vivo Differentiation of Human Male Germ Cell Tumors
Research Article Down-Regulation of Stem Cell Genes, Including Those in a 200-kb Gene Cluster at 12p13.31, Is Associated with In vivo Differentiation of Human Male Germ Cell Tumors James E. Korkola,1 Jane Houldsworth,1,2 Rajendrakumar S.V. Chadalavada,1 Adam B. Olshen,3 Debbie Dobrzynski,2 Victor E. Reuter,4 George J. Bosl,2 and R.S.K. Chaganti1,2 1Cell Biology Program and Departments of 2Medicine, 3Epidemiology and Biostatistics, and 4Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York Abstract on the degree and type of differentiation (i.e., seminomas, which Adult male germ cell tumors (GCTs) comprise distinct groups: resemble undifferentiated primitive germ cells, and nonseminomas, seminomas and nonseminomas, which include pluripotent which show varying degrees of embryonic and extraembryonic embryonal carcinomas as well as other histologic subtypes patterns of differentiation; refs. 2, 3). Nonseminomatous GCTs are exhibiting various stages of differentiation. Almost all GCTs further subdivided into embryonal carcinomas, which show early show 12p gain, but the target genes have not been clearly zygotic or embryonal-like differentiation, yolk sac tumors and defined. To identify 12p target genes, we examined Affymetrix choriocarcinomas, which exhibit extraembryonal forms of differ- (Santa Clara, CA) U133A+B microarray (f83% coverage of 12p entiation, and teratomas, which show somatic differentiation along genes) expression profiles of 17 seminomas, 84 nonseminoma multiple lineages (3). Both seminomas and embryonal carcinoma GCTs, and 5 normal testis samples. Seventy-three genes on 12p are known to express stem cell markers, such as POU5F1 (4) and were significantly overexpressed, including GLUT3 and REA NANOG (5). -
Derivation of Stable Microarray Cancer-Differentiating Signatures Using Consensus Scoring of Multiple Random Sampling and Gene-Ranking Consistency Evaluation
Research Article Derivation of Stable Microarray Cancer-Differentiating Signatures Using Consensus Scoring of Multiple Random Sampling and Gene-Ranking Consistency Evaluation Zhi Qun Tang,1,2 Lian Yi Han,1,2 Hong Huang Lin,1,2 Juan Cui,1,2 Jia Jia,1,2 Boon Chuan Low,2,3 Bao Wen Li,2,4 and Yu Zong Chen1,2 1Bioinformatics and Drug Design Group, Department of Pharmacy; 2Center for Computational Science and Engineering; and Departments of 3Biological Sciences and 4Physics, National University of Singapore, Singapore, Singapore Abstract sampling methods. Only 1 to 5 of the 4 to 60 selected predictor Microarrays have been explored for deriving molecular genes in each of these sets are present in more than half of the signatures to determine disease outcomes, mechanisms, other nine sets (Table 1), and 2 to 20 of the predictor genes in each targets, and treatment strategies. Although exhibiting good set are cancer related (Table 2). Despite the use of sophisticated predictive performance, some derived signatures are unstable class differentiation and signature selection methods, the selected due to noises arising from measurement variability and signatures show few overlapping predictor genes, as in the case of biological differences. Improvements in measurement, anno- other microarray data sets including non–Hodgkin lymphoma, tation, and signature selection methods have been proposed. acute lymphocytic leukemia, breast cancer, lung adenocarcinoma, We explored a new signature selection method that incorpo- medulloblastoma, hepatocellular carcinoma, and acute myeloid rates consensus scoring of multiple random sampling and leukemia (9, 15). multistep evaluation of gene-ranking consistency for maxi- Although these signatures display high cancer differentiation mally avoiding erroneous elimination of predictor genes. -
Sanjay Kumar Gupta
The human CCHC-type Zinc Finger Nucleic Acid Binding Protein (CNBP) binds to the G-rich elements in target mRNA coding sequences and promotes translation Das humane CCHC-Typ-Zinkfinger-Nukleinsäure-Binde-Protein (CNBP) bindet an G-reiche Elemente in der kodierenden Sequenz seiner Ziel-mRNAs und fördert deren Translation Doctoral thesis for a doctoral degree at the Graduate School of Life Sciences, Julius-Maximilians-Universität WürzBurg, Section: Biomedicine suBmitted By Sanjay Kumar Gupta from Varanasi, India WürzBurg, 2016 1 Submitted on: …………………………………………………………..…….. Office stamp Members of the Promotionskomitee: Chairperson: Prof. Dr. Alexander Buchberger Primary Supervisor: Dr. Stefan Juranek Supervisor (Second): Prof. Dr. Utz Fischer Supervisor (Third): Dr. Markus Landthaler Date of Public Defence: …………………………………………….………… Date of Receipt of Certificates: ………………………………………………. 2 Summary The genetic information encoded with in the genes are transcribed and translated to give rise to the functional proteins, which are building block of a cell. At first, it was thought that the regulation of gene expression particularly occurs at the level of transcription By various transcription factors. Recent discoveries have shown the vital role of gene regulation at the level of RNA also known as post-transcriptional gene regulation (PTGR). Apart from non-coding RNAs e.g. micro RNAs, various RNA Binding proteins (RBPs) play essential role in PTGR. RBPs have been implicated in different stages of mRNA life cycle ranging from splicing, processing, transport, localization and decay. In last 20 years studies have shown the presence of hundreds of RBPs across eukaryotic systems many of which are widely conserved. Given the rising numBer of RBPs and their link to human diseases it is quite evident that RBPs have major role in cellular processes and their regulation. -
Ovarian Gene Expression in the Absence of FIGLA, an Oocyte
BMC Developmental Biology BioMed Central Research article Open Access Ovarian gene expression in the absence of FIGLA, an oocyte-specific transcription factor Saurabh Joshi*1, Holly Davies1, Lauren Porter Sims2, Shawn E Levy2 and Jurrien Dean1 Address: 1Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA and 2Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37232, USA Email: Saurabh Joshi* - [email protected]; Holly Davies - [email protected]; Lauren Porter Sims - [email protected]; Shawn E Levy - [email protected]; Jurrien Dean - [email protected] * Corresponding author Published: 13 June 2007 Received: 11 December 2006 Accepted: 13 June 2007 BMC Developmental Biology 2007, 7:67 doi:10.1186/1471-213X-7-67 This article is available from: http://www.biomedcentral.com/1471-213X/7/67 © 2007 Joshi et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Ovarian folliculogenesis in mammals is a complex process involving interactions between germ and somatic cells. Carefully orchestrated expression of transcription factors, cell adhesion molecules and growth factors are required for success. We have identified a germ-cell specific, basic helix-loop-helix transcription factor, FIGLA (Factor In the GermLine, Alpha) and demonstrated its involvement in two independent developmental processes: formation of the primordial follicle and coordinate expression of zona pellucida genes. Results: Taking advantage of Figla null mouse lines, we have used a combined approach of microarray and Serial Analysis of Gene Expression (SAGE) to identify potential downstream target genes. -
The Zinc-Finger Protein CNBP Is Required for Forebrain Formation In
Development 130, 1367-1379 1367 © 2003 The Company of Biologists Ltd doi:10.1242/dev.00349 The zinc-finger protein CNBP is required for forebrain formation in the mouse Wei Chen1,2, Yuqiong Liang1, Wenjie Deng1, Ken Shimizu1, Amir M. Ashique1,2, En Li3 and Yi-Ping Li1,2,* 1Department of Cytokine Biology, The Forsyth Institute, Boston, MA 02115, USA 2Harvard-Forsyth Department of Oral Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA 3Cardiovascular Research Center, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA *Author for correspondence (e-mail: [email protected]) Accepted 19 December 2002 SUMMARY Mouse mutants have allowed us to gain significant insight (AME), headfolds and forebrain. In Cnbp–/– embryos, the into axis development. However, much remains to be visceral endoderm remains in the distal tip of the conceptus learned about the cellular and molecular basis of early and the ADE fails to form, whereas the node and notochord forebrain patterning. We describe a lethal mutation mouse form normally. A substantial reduction in cell proliferation strain generated using promoter-trap mutagenesis. The was observed in the anterior regions of Cnbp–/– embryos at mutants exhibit severe forebrain truncation in homozygous gastrulation and neural-fold stages. In these regions, Myc mouse embryos and various craniofacial defects in expression was absent, indicating CNBP targets Myc in heterozygotes. We show that the defects are caused by rostral head formation. Our findings demonstrate that disruption of the gene encoding cellular nucleic acid Cnbp is essential for the forebrain induction and binding protein (CNBP); Cnbp transgenic mice were able specification. -
Aquaporin Channels in the Heart—Physiology and Pathophysiology
International Journal of Molecular Sciences Review Aquaporin Channels in the Heart—Physiology and Pathophysiology Arie O. Verkerk 1,2,* , Elisabeth M. Lodder 2 and Ronald Wilders 1 1 Department of Medical Biology, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; [email protected] 2 Department of Experimental Cardiology, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; [email protected] * Correspondence: [email protected]; Tel.: +31-20-5664670 Received: 29 March 2019; Accepted: 23 April 2019; Published: 25 April 2019 Abstract: Mammalian aquaporins (AQPs) are transmembrane channels expressed in a large variety of cells and tissues throughout the body. They are known as water channels, but they also facilitate the transport of small solutes, gasses, and monovalent cations. To date, 13 different AQPs, encoded by the genes AQP0–AQP12, have been identified in mammals, which regulate various important biological functions in kidney, brain, lung, digestive system, eye, and skin. Consequently, dysfunction of AQPs is involved in a wide variety of disorders. AQPs are also present in the heart, even with a specific distribution pattern in cardiomyocytes, but whether their presence is essential for proper (electro)physiological cardiac function has not intensively been studied. This review summarizes recent findings and highlights the involvement of AQPs in normal and pathological cardiac function. We conclude that AQPs are at least implicated in proper cardiac water homeostasis and energy balance as well as heart failure and arsenic cardiotoxicity. However, this review also demonstrates that many effects of cardiac AQPs, especially on excitation-contraction coupling processes, are virtually unexplored. -
Structural Characterization of Polysaccharides from Cordyceps Militaris and Their Hypolipidemic Effects Cite This: RSC Adv.,2018,8,41012 in High Fat Diet Fed Mice†
RSC Advances View Article Online PAPER View Journal | View Issue Structural characterization of polysaccharides from Cordyceps militaris and their hypolipidemic effects Cite this: RSC Adv.,2018,8,41012 in high fat diet fed mice† Zhen-feng Huang, ‡ Ming-long Zhang,‡ Song Zhang,* Ya-hui Wang and Xue-wen Jiang Cordyceps militaris is a crude dietary therapeutic mushroom with high nutritional and medicinal values. Mushroom-derived polysaccharides have been found to possess antihyperglycemic and antihyperlipidemic activities. This study aimed to partially clarify the structural characterization and comparatively evaluate hypolipidemic potentials of intracellular- (IPCM) and extracellular polysaccharides of C. militaris (EPCM) in high fat diet fed mice. Results indicated that IPCM-2 is a-pyran polysaccharide with an average molecular weight of 32.5 kDa, was mainly composed of mannose, glucose and galactose with mass percentages of 51.94%, 10.54%, and 37.25%, respectively. EPCM-2 is an a-pyran Creative Commons Attribution 3.0 Unported Licence. polysaccharide with an average molecular weight of 20 kDa that is mainly composed of mannose, glucose and galactose with mass percentages of 44.51%, 18.33%, and 35.38%, respectively. In in vivo study, EPCM-1 treatment (100 mg kgÀ1 dÀ1) showed potential effects on improving serum lipid profiles of hyperlipidemic mice, reflected by decreasing serum total cholesterol (TC), triglyceride (TG) and low density lipoprotein-cholesterol (LDL-C) levels by 20.05%, 45.45% and 52.63%, respectively, while IPCM-1 treatment -
C-Myc Regulates Cell Proliferation During Lens Development
c-myc Regulates Cell Proliferation during Lens Development Gabriel R. Cavalheiro., Gabriel E. Matos-Rodrigues., Anielle L. Gomes, Paulo M. G. Rodrigues, Rodrigo A. P. Martins* Programa de Biologia Celular e do Desenvolvimento, Instituto de Cieˆncias Biome´dicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil Abstract Myc protooncogenes play important roles in the regulation of cell proliferation, growth, differentiation and survival during development. In various developing organs, c-myc has been shown to control the expression of cell cycle regulators and its misregulated expression is detected in many human tumors. Here, we show that c-myc gene (Myc) is highly expressed in developing mouse lens. Targeted deletion of c-myc gene from head surface ectoderm dramatically impaired ocular organogenesis, resulting in severe microphtalmia, defective anterior segment development, formation of a lens stalk and/or aphakia. In particular, lenses lacking c-myc presented thinner epithelial cell layer and growth impairment that was detectable soon after its inactivation. Defective development of c-myc-null lens was not caused by increased cell death of lens progenitor cells. Instead, c-myc loss reduced cell proliferation, what was associated with an ectopic expression of Prox1 and p27Kip1 proteins within epithelial cells. Interestingly, a sharp decrease in the expression of the forkhead box transcription factor Foxe3 was also observed following c-myc inactivation. These data represent the first description of the physiological roles played by a Myc family member in mouse lens development. Our findings support the conclusion that c- myc regulates the proliferation of lens epithelial cells in vivo and may, directly or indirectly, modulate the expression of classical cell cycle regulators in developing mouse lens. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
TNAP As a New Player in Chronic Inflammatory Conditions And
International Journal of Molecular Sciences Review TNAP as a New Player in Chronic Inflammatory Conditions and Metabolism Stephanie Graser 1,*, Daniel Liedtke 2,† and Franz Jakob 1,† 1 Bernhard-Heine-Center for Locomotion Research, Department of Orthopedics, Julius-Maximilians-University Würzburg, 97076 Würzburg, Germany; [email protected] 2 Institute for Human Genetics, Biocenter, Julius-Maximilians-University Würzburg, 97074 Würzburg, Germany; [email protected] * Correspondence: [email protected] † These authors contributed equally to this work. Abstract: This review summarizes important information on the ectoenzyme tissue-nonspecific alkaline phosphatase (TNAP) and gives a brief insight into the symptoms, diagnostics, and treatment of the rare disease Hypophosphatasia (HPP), which is resulting from mutations in the TNAP encoding ALPL gene. We emphasize the role of TNAP beyond its well-known contribution to mineralization processes. Therefore, above all, the impact of the enzyme on central molecular processes in the nervous system and on inflammation is presented here. Keywords: TNAP; Hypophosphatasia; HPP; mineralization; nervous system; inflammation 1. Structure, Function, and Substrates of TNAP Tissue-nonspecific alkaline phosphatase (TNAP) or liver/bone/kidney alkaline phos- phatase is an ectoenzyme that is anchored to the outer cell membrane (e.g. in osteoblasts) Citation: Graser, S.; Liedtke, D.; and to extracellular vesicles via its glycosyl-inositol-phosphate (GPI)-anchor [1,2]. TNAP Jakob, F. TNAP as a New Player in belongs to the family of alkaline phosphatases (AP) that comprises in humans three addi- Chronic Inflammatory Conditions tional tissue-specific isoforms: placental (PLAP, ALPP National Center for Biotechnology and Metabolism. Int. -
Emerging Roles for Multifunctional Ion Channel Auxiliary Subunits in Cancer T ⁎ Alexander S
Cell Calcium 80 (2019) 125–140 Contents lists available at ScienceDirect Cell Calcium journal homepage: www.elsevier.com/locate/ceca Emerging roles for multifunctional ion channel auxiliary subunits in cancer T ⁎ Alexander S. Hawortha,b, William J. Brackenburya,b, a Department of Biology, University of York, Heslington, York, YO10 5DD, UK b York Biomedical Research Institute, University of York, Heslington, York, YO10 5DD, UK ARTICLE INFO ABSTRACT Keywords: Several superfamilies of plasma membrane channels which regulate transmembrane ion flux have also been Auxiliary subunit shown to regulate a multitude of cellular processes, including proliferation and migration. Ion channels are Cancer typically multimeric complexes consisting of conducting subunits and auxiliary, non-conducting subunits. Calcium channel Auxiliary subunits modulate the function of conducting subunits and have putative non-conducting roles, further Chloride channel expanding the repertoire of cellular processes governed by ion channel complexes to processes such as trans- Potassium channel cellular adhesion and gene transcription. Given this expansive influence of ion channels on cellular behaviour it Sodium channel is perhaps no surprise that aberrant ion channel expression is a common occurrence in cancer. This review will − focus on the conducting and non-conducting roles of the auxiliary subunits of various Ca2+,K+,Na+ and Cl channels and the burgeoning evidence linking such auxiliary subunits to cancer. Several subunits are upregu- lated (e.g. Cavβ,Cavγ) and downregulated (e.g. Kvβ) in cancer, while other subunits have been functionally implicated as oncogenes (e.g. Navβ1,Cavα2δ1) and tumour suppressor genes (e.g. CLCA2, KCNE2, BKγ1) based on in vivo studies. The strengthening link between ion channel auxiliary subunits and cancer has exposed these subunits as potential biomarkers and therapeutic targets. -
A Genetic Overview of Hypophosphatasia a Background in Genetics
A Genetic Overview of Hypophosphatasia A Background in Genetics Cells are the basic building blocks of all living organisms. Our body is composed of trillions of cells. Each of these cells contains deoxyribonucleic acid (DNA), the hereditary material. DNA contains genetic instructions and tells the cell what to do and how to grow. DNA is stored in chromosomes. Humans have 23 pairs of chromosomes - a total of 46 - and each pair is labeled with its own number or letter for the X and Y sex chromosomes. Each set of chromosomes comes from each of our parents. » Cell Components Lisa Ormerod.1 Genes are located on chromosomes and determine our physical features. Genes are made up of DNA and they make molecules called proteins, the building blocks of all structures in the body. A Background in Genetics (continued) In the human body every gene contains a code that acts as a blueprint for the cell. Cells use this blueprint to make a certain protein that is necessary to keep our bodies healthy. Every person has two copies of each gene, one inherited from each parent. Genes are made up of combinations of nucleic acids: Adenine (A), Thymine (T), Cytosine (C) and Guanine (G). The genetic blueprint determines how these letters come together and form the DNA structure called the double helix, which resembles a twisted ladder. The order, or sequence, of these nucleic acids determines what biological instructions are contained in a strand of DNA, similar to how letters of the alphabet form words. » Nucleic Acids Cytosine Base pair Guanine Adenine Helix of sugar-phosphates Thymine Nucleobases of DNA DNA Deoxyribonucleic acid Adapted from: Chemical structures of nucleobases by Roland1952.2 » DNA Mutations Sometimes there are mistakes or changes in the pattern of letters in the DNA sequence.