Differential Immune Response Modulation in Early Leishmania
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University of California, San Diego
UNIVERSITY OF CALIFORNIA, SAN DIEGO The post-terminal differentiation fate of RNAs revealed by next-generation sequencing A dissertation submitted in partial satisfaction of the requirements for the degree Doctor of Philosophy in Biomedical Sciences by Gloria Kuo Lefkowitz Committee in Charge: Professor Benjamin D. Yu, Chair Professor Richard Gallo Professor Bruce A. Hamilton Professor Miles F. Wilkinson Professor Eugene Yeo 2012 Copyright Gloria Kuo Lefkowitz, 2012 All rights reserved. The Dissertation of Gloria Kuo Lefkowitz is approved, and it is acceptable in quality and form for publication on microfilm and electronically: __________________________________________________________________ __________________________________________________________________ __________________________________________________________________ __________________________________________________________________ __________________________________________________________________ Chair University of California, San Diego 2012 iii DEDICATION Ma and Ba, for your early indulgence and support. Matt and James, for choosing more practical callings. Roy, my love, for patiently sharing the ups and downs of this journey. iv EPIGRAPH It is foolish to tear one's hair in grief, as though sorrow would be made less by baldness. ~Cicero v TABLE OF CONTENTS Signature Page .............................................................................................................. iii Dedication .................................................................................................................... -
Activated Peripheral-Blood-Derived Mononuclear Cells
Transcription factor expression in lipopolysaccharide- activated peripheral-blood-derived mononuclear cells Jared C. Roach*†, Kelly D. Smith*‡, Katie L. Strobe*, Stephanie M. Nissen*, Christian D. Haudenschild§, Daixing Zhou§, Thomas J. Vasicek¶, G. A. Heldʈ, Gustavo A. Stolovitzkyʈ, Leroy E. Hood*†, and Alan Aderem* *Institute for Systems Biology, 1441 North 34th Street, Seattle, WA 98103; ‡Department of Pathology, University of Washington, Seattle, WA 98195; §Illumina, 25861 Industrial Boulevard, Hayward, CA 94545; ¶Medtronic, 710 Medtronic Parkway, Minneapolis, MN 55432; and ʈIBM Computational Biology Center, P.O. Box 218, Yorktown Heights, NY 10598 Contributed by Leroy E. Hood, August 21, 2007 (sent for review January 7, 2007) Transcription factors play a key role in integrating and modulating system. In this model system, we activated peripheral-blood-derived biological information. In this study, we comprehensively measured mononuclear cells, which can be loosely termed ‘‘macrophages,’’ the changing abundances of mRNAs over a time course of activation with lipopolysaccharide (LPS). We focused on the precise mea- of human peripheral-blood-derived mononuclear cells (‘‘macro- surement of mRNA concentrations. There is currently no high- phages’’) with lipopolysaccharide. Global and dynamic analysis of throughput technology that can precisely and sensitively measure all transcription factors in response to a physiological stimulus has yet to mRNAs in a system, although such technologies are likely to be be achieved in a human system, and our efforts significantly available in the near future. To demonstrate the potential utility of advanced this goal. We used multiple global high-throughput tech- such technologies, and to motivate their development and encour- nologies for measuring mRNA levels, including massively parallel age their use, we produced data from a combination of two distinct signature sequencing and GeneChip microarrays. -
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. -
Genome-Wide Analysis of Allele-Specific Expression Patterns in Seventeen Tissues of Korean Cattle (Hanwoo)
animals Article Genome-Wide Analysis of Allele-Specific Expression Patterns in Seventeen Tissues of Korean Cattle (Hanwoo) Kyu-Sang Lim 1 , Sun-Sik Chang 2, Bong-Hwan Choi 3, Seung-Hwan Lee 4, Kyung-Tai Lee 3 , Han-Ha Chai 3, Jong-Eun Park 3 , Woncheoul Park 3 and Dajeong Lim 3,* 1 Department of Animal Science, Iowa State University, Ames, IA 50011, USA; [email protected] 2 Hanwoo Research Institute, National Institute of Animal Science, Rural Development Administration, Pyeongchang 25340, Korea; [email protected] 3 Animal Genomics and Bioinformatics Division, National Institute of Animal Science, Rural Development Administration, Wanju 55365, Korea; [email protected] (B.-H.C.); [email protected] (K.-T.L.); [email protected] (H.-H.C.); [email protected] (J.-E.P.); [email protected] (W.P.) 4 Division of Animal and Dairy Science, Chungnam National University, Daejeon 34134, Korea; [email protected] * Correspondence: [email protected] Received: 26 July 2019; Accepted: 23 September 2019; Published: 26 September 2019 Simple Summary: Allele-specific expression (ASE) is the biased allelic expression of genetic variants within the gene. Recently, the next-generation sequencing (NGS) technologies allowed us to detect ASE genes at a transcriptome-wide level. It is essential for the understanding of animal development, cellular programming, and the effect on their complexity because ASE shows developmental, tissue, or species-specific patterns. However, these aspects of ASE still have not been annotated well in farm animals and most studies were conducted mainly at the fetal stages. Hence, the current study focuses on detecting ASE genes in 17 tissues in adult cattle. -
Prospective Isolation of NKX2-1–Expressing Human Lung Progenitors Derived from Pluripotent Stem Cells
The Journal of Clinical Investigation RESEARCH ARTICLE Prospective isolation of NKX2-1–expressing human lung progenitors derived from pluripotent stem cells Finn Hawkins,1,2 Philipp Kramer,3 Anjali Jacob,1,2 Ian Driver,4 Dylan C. Thomas,1 Katherine B. McCauley,1,2 Nicholas Skvir,1 Ana M. Crane,3 Anita A. Kurmann,1,5 Anthony N. Hollenberg,5 Sinead Nguyen,1 Brandon G. Wong,6 Ahmad S. Khalil,6,7 Sarah X.L. Huang,3,8 Susan Guttentag,9 Jason R. Rock,4 John M. Shannon,10 Brian R. Davis,3 and Darrell N. Kotton1,2 2 1Center for Regenerative Medicine, and The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA. 3Center for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA. 4Department of Anatomy, UCSF, San Francisco, California, USA. 5Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA. 6Department of Biomedical Engineering and Biological Design Center, Boston University, Boston, Massachusetts, USA. 7Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA. 8Columbia Center for Translational Immunology & Columbia Center for Human Development, Columbia University Medical Center, New York, New York, USA. 9Department of Pediatrics, Monroe Carell Jr. Children’s Hospital, Vanderbilt University, Nashville, Tennessee, USA. 10Division of Pulmonary Biology, Cincinnati Children’s Hospital, Cincinnati, Ohio, USA. It has been postulated that during human fetal development, all cells of the lung epithelium derive from embryonic, endodermal, NK2 homeobox 1–expressing (NKX2-1+) precursor cells. -
Leishmania\) Martiniquensis N. Sp. \(Kinetoplastida: Trypanosomatidae\
Parasite 2014, 21, 12 Ó N. Desbois et al., published by EDP Sciences, 2014 DOI: 10.1051/parasite/2014011 urn:lsid:zoobank.org:pub:31F25656-8804-4944-A568-6DB4F52D2217 Available online at: www.parasite-journal.org SHORT NOTE OPEN ACCESS Leishmania (Leishmania) martiniquensis n. sp. (Kinetoplastida: Trypanosomatidae), description of the parasite responsible for cutaneous leishmaniasis in Martinique Island (French West Indies) Nicole Desbois1, Francine Pratlong2, Danie`le Quist3, and Jean-Pierre Dedet2,* 1 CHU de la Martinique, Hoˆpital Pierre-Zobda-Quitman, Poˆle de Biologie de territoire-Pathologie, Unite´de Parasitologie-Mycologie, BP 632, 97261 Fort-de-France Cedex, Martinique, France 2 Universite´Montpellier 1 et CHRU de Montpellier, Centre National de re´fe´rence des leishmanioses, UMR « MIVEGEC » (CNRS 5290, IRD 224, UM1, UM2), De´partement de Parasitologie-Mycologie (Professeur Patrick Bastien), 39 avenue Charles Flahault, 34295 Montpellier Cedex 5, France 3 CHU de la Martinique, Hoˆpital Pierre-Zobda-Quitman, Service de dermatologie, Poˆle de Me´decine-Spe´cialite´s me´dicales, BP 632, 97261 Fort-de-France Cedex, Martinique, France Received 21 November 2013, Accepted 19 February 2014, Published online 14 March 2014 Abstract – The parasite responsible for autochthonous cutaneous leishmaniasis in Martinique island (French West Indies) was first isolated in 1995; its taxonomical position was established only in 2002, but it remained unnamed. In the present paper, the authors name this parasite Leishmania (Leishmania) martiniquensis Desbois, Pratlong & Dedet n. sp. and describe the type strain of this taxon, including its biological characteristics, biochemical and molecular identification, and pathogenicity. This parasite, clearly distinct from all other Euleishmania, and placed at the base of the Leishmania phylogenetic tree, is included in the subgenus Leishmania. -
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. -
DNA Methylation Changes in Down Syndrome Derived Neural Ipscs Uncover Co-Dysregulation of ZNF and HOX3 Families of Transcription
Laan et al. Clinical Epigenetics (2020) 12:9 https://doi.org/10.1186/s13148-019-0803-1 RESEARCH Open Access DNA methylation changes in Down syndrome derived neural iPSCs uncover co- dysregulation of ZNF and HOX3 families of transcription factors Loora Laan1†, Joakim Klar1†, Maria Sobol1, Jan Hoeber1, Mansoureh Shahsavani2, Malin Kele2, Ambrin Fatima1, Muhammad Zakaria1, Göran Annerén1, Anna Falk2, Jens Schuster1 and Niklas Dahl1* Abstract Background: Down syndrome (DS) is characterized by neurodevelopmental abnormalities caused by partial or complete trisomy of human chromosome 21 (T21). Analysis of Down syndrome brain specimens has shown global epigenetic and transcriptional changes but their interplay during early neurogenesis remains largely unknown. We differentiated induced pluripotent stem cells (iPSCs) established from two DS patients with complete T21 and matched euploid donors into two distinct neural stages corresponding to early- and mid-gestational ages. Results: Using the Illumina Infinium 450K array, we assessed the DNA methylation pattern of known CpG regions and promoters across the genome in trisomic neural iPSC derivatives, and we identified a total of 500 stably and differentially methylated CpGs that were annotated to CpG islands of 151 genes. The genes were enriched within the DNA binding category, uncovering 37 factors of importance for transcriptional regulation and chromatin structure. In particular, we observed regional epigenetic changes of the transcription factor genes ZNF69, ZNF700 and ZNF763 as well as the HOXA3, HOXB3 and HOXD3 genes. A similar clustering of differential methylation was found in the CpG islands of the HIST1 genes suggesting effects on chromatin remodeling. Conclusions: The study shows that early established differential methylation in neural iPSC derivatives with T21 are associated with a set of genes relevant for DS brain development, providing a novel framework for further studies on epigenetic changes and transcriptional dysregulation during T21 neurogenesis. -
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Supplementary Figure S1. Results of flow cytometry analysis, performed to estimate CD34 positivity, after immunomagnetic separation in two different experiments. As monoclonal antibody for labeling the sample, the fluorescein isothiocyanate (FITC)- conjugated mouse anti-human CD34 MoAb (Mylteni) was used. Briefly, cell samples were incubated in the presence of the indicated MoAbs, at the proper dilution, in PBS containing 5% FCS and 1% Fc receptor (FcR) blocking reagent (Miltenyi) for 30 min at 4 C. Cells were then washed twice, resuspended with PBS and analyzed by a Coulter Epics XL (Coulter Electronics Inc., Hialeah, FL, USA) flow cytometer. only use Non-commercial 1 Supplementary Table S1. Complete list of the datasets used in this study and their sources. GEO Total samples Geo selected GEO accession of used Platform Reference series in series samples samples GSM142565 GSM142566 GSM142567 GSM142568 GSE6146 HG-U133A 14 8 - GSM142569 GSM142571 GSM142572 GSM142574 GSM51391 GSM51392 GSE2666 HG-U133A 36 4 1 GSM51393 GSM51394 only GSM321583 GSE12803 HG-U133A 20 3 GSM321584 2 GSM321585 use Promyelocytes_1 Promyelocytes_2 Promyelocytes_3 Promyelocytes_4 HG-U133A 8 8 3 GSE64282 Promyelocytes_5 Promyelocytes_6 Promyelocytes_7 Promyelocytes_8 Non-commercial 2 Supplementary Table S2. Chromosomal regions up-regulated in CD34+ samples as identified by the LAP procedure with the two-class statistics coded in the PREDA R package and an FDR threshold of 0.5. Functional enrichment analysis has been performed using DAVID (http://david.abcc.ncifcrf.gov/) -
Integrative Genome Analysis of Somatic P53 Mutant Osteosarcomas Identifies Ets2-Dependent Regulation of Small Nucleolar Rnas by Mutant P53 Protein
Downloaded from genesdev.cshlp.org on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press Integrative genome analysis of somatic p53 mutant osteosarcomas identifies Ets2-dependent regulation of small nucleolar RNAs by mutant p53 protein Rasoul Pourebrahim,1 Yun Zhang,1 Bin Liu,1 Ruli Gao,1 Shunbin Xiong,1 Patrick P. Lin,2 Mark J. McArthur,3 Michael C. Ostrowski,4 and Guillermina Lozano1 1Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; 2Department of Orthopedic Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; 3Department of Veterinary Medicine and Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; 4Department of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio 43210, USA TP53 is the most frequently mutated gene in human cancer. Many mutant p53 proteins exert oncogenic gain-of- function (GOF) properties that contribute to metastasis, but the mechanisms mediating these functions remain poorly defined in vivo. To elucidate how mutant p53 GOF drives metastasis, we developed a traceable somatic os- teosarcoma mouse model that is initiated with either a single p53 mutation (p53R172H) or p53 loss in osteoblasts. Our study confirmed that p53 mutant mice developed osteosarcomas with increased metastasis as compared with p53-null mice. Comprehensive transcriptome RNA sequencing (RNA-seq) analysis of 16 tumors identified a cluster of small nucleolar RNAs (snoRNAs) that are highly up-regulated in p53 mutant tumors. Regulatory element analysis of these deregulated snoRNA genes identified strong enrichment of a common Ets2 transcription factor-binding site. Homozygous deletion of Ets2 in p53 mutant mice resulted in strong down-regulation of snoRNAs and reversed the prometastatic phenotype of mutant p53 but had no effect on osteosarcoma development, which remained 100% penetrant. -
Mapping the Genetic Architecture of Gene Regulation in Whole Blood
Mapping the Genetic Architecture of Gene Regulation in Whole Blood Katharina Schramm1,2., Carola Marzi3,4,5., Claudia Schurmann6., Maren Carstensen7,8., Eva Reinmaa9,10, Reiner Biffar11, Gertrud Eckstein1, Christian Gieger12, Hans-Jo¨ rgen Grabe13, Georg Homuth6, Gabriele Kastenmu¨ ller14, Reedik Ma¨gi10, Andres Metspalu9,10, Evelin Mihailov10,15, Annette Peters2, Astrid Petersmann16, Michael Roden7,8,17, Konstantin Strauch12,18, Karsten Suhre14,19, Alexander Teumer6,UweVo¨ lker6, Henry Vo¨ lzke20, Rui Wang-Sattler3,4, Melanie Waldenberger3,4, Thomas Meitinger1,2,21, Thomas Illig22, Christian Herder7,8., Harald Grallert3,4,5., Holger Prokisch1,2*. 1 Institute of Human Genetics, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany, 2 Institute of Human Genetics, Technical University Munich, Mu¨nchen, Germany, 3 Research Unit of Molecular Epidemiology, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany, 4 Institute of Epidemiology II, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany, 5 German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany, 6 Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany, 7 Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Du¨sseldorf, Du¨sseldorf, Germany, 8 German Center for Diabetes Research (DZD e.V.), -
Thyroid Gland Development and Function in the Zebrafish Model P
THYROID GLAND DEVELOPMENT AND FUNCTION IN THE ZEBRAFISH MODEL P. Porazzi, D. Calebiro, F. Benato, N. Tiso, L. Persani To cite this version: P. Porazzi, D. Calebiro, F. Benato, N. Tiso, L. Persani. THYROID GLAND DEVELOPMENT AND FUNCTION IN THE ZEBRAFISH MODEL. Molecular and Cellular Endocrinology, Elsevier, 2009, 312 (1-2), pp.14. 10.1016/j.mce.2009.05.011. hal-00521550 HAL Id: hal-00521550 https://hal.archives-ouvertes.fr/hal-00521550 Submitted on 28 Sep 2010 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Accepted Manuscript Title: THYROID GLAND DEVELOPMENT AND FUNCTION IN THE ZEBRAFISH MODEL Authors: P. Porazzi, D. Calebiro, F. Benato, N. Tiso, L. Persani PII: S0303-7207(09)00277-9 DOI: doi:10.1016/j.mce.2009.05.011 Reference: MCE 7224 To appear in: Molecular and Cellular Endocrinology Received date: 6-3-2009 Revised date: 20-5-2009 Accepted date: 20-5-2009 Please cite this article as: Porazzi, P., Calebiro, D., Benato, F., Tiso, N., Persani, L., THYROID GLAND DEVELOPMENT AND FUNCTION IN THE ZEBRAFISH MODEL, Molecular and Cellular Endocrinology (2008), doi:10.1016/j.mce.2009.05.011 This is a PDF file of an unedited manuscript that has been accepted for publication.