DOCSLIB.ORG

Embryonic Kidney Development, Stem Cells and the Origin of Wilms Tumor

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Embryonic Kidney Development, Stem Cells and the Origin of Wilms Tumor G C A T T A C G G C A T genes Review Embryonic Kidney Development, Stem Cells and the Origin of Wilms Tumor Hao Li 1, Peter Hohenstein 2 and Satu Kuure 1,3,* 1 Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, FIN-00014 Helsinki, Finland; hao.li@helsinki.fi 2 Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; [email protected] 3 GM-Unit, Laboratory Animal Center, Helsinki Institute of Life Science, University of Helsinki, FIN-00014 Helsinki, Finland * Correspondence: satu.kuure@helsinki.fi; Tel.: +358-2941-59395 Abstract: The adult mammalian kidney is a poorly regenerating organ that lacks the stem cells that could replenish functional homeostasis similarly to, e.g., skin or the hematopoietic system. Unlike a mature kidney, the embryonic kidney hosts at least three types of lineage-specific stem cells that give rise to (a) a ureter and collecting duct system, (b) nephrons, and (c) mesangial cells together with connective tissue of the stroma. Extensive interest has been raised towards these embryonic progenitor cells, which are normally lost before birth in humans but remain part of the undifferentiated nephrogenic rests in the pediatric renal cancer Wilms tumor. Here, we discuss the current understanding of kidney-specific embryonic progenitor regulation in the innate environment of the developing kidney and the types of disruptions in their balanced regulation that lead to the formation of Wilms tumor. Keywords: kidney; organogenesis; pediatric cancer; stem cells; differentiation; self-renewal Citation: Li, H.; Hohenstein, P.; Kuure, S. Embryonic Kidney Development, Stem Cells and the Origin of Wilms Tumor. Genes 2021, 1. Introduction 12, 318. https://doi.org/10.3390/ genes12020318 Stem cells form a fundamental basis not only for normal development and tissue homeostasis but also for tumorigenesis. The adult mammalian kidney is mostly devoid of Academic Editor: Simona Chera stem cells and is thus considered a non-regenerative organ, especially when regeneration is defined by the ability to generate new nephrons and regain filtration capacity [1]. Contrary Received: 27 January 2021 to this, the embryonic kidney hosts at least three types of lineage-specific stem cells (referred Accepted: 18 February 2021 to here as progenitors) that give rise to the ureter and collecting duct system, nephrons, Published: 23 February 2021 and the connective tissue of the stroma [2,3]. These progenitor cells have raised substantial interest for use in regeneration-based renal medicine, but the safety of the undifferentiated Publisher’s Note: MDPI stays neutral cell maintenance in postnatal kidneys is a significantly less discussed topic. with regard to jurisdictional claims in An integral part of the safety assessment is a thorough understanding of tissue- published maps and institutional affil- residing progenitor regulation. The mechanisms guiding the maintenance and differen- iations. tiation of tissue-specific progenitors are aberrantly reactivated in many cancers [4]. This is especially obvious in embryonic-derived tumors such as Wilms tumor (WT; Figure1), medulloblastoma, and retinoblastoma. Nephrons—the functional filtration units of mammalian kidneys—and renal stroma Copyright: © 2021 by the authors. are derived from metanephric mesenchyme containing distinct progenitor pools for both Licensee MDPI, Basel, Switzerland. lineages [5,6]. Metanephric tissue is normally lost before birth in humans but remains part This article is an open access article of the undifferentiated nephrogenic rests in Wilms tumor patients [7,8]. Understanding distributed under the terms and the differences between normal tissue-residing progenitors and cancer-causing stem cells conditions of the Creative Commons is required to set the stage for better characterization of transformations that turn normal Attribution (CC BY) license (https:// kidney progenitors into Wilms tumor stem cells. This may essentially help with predict- creativecommons.org/licenses/by/ ing individualized disease prognosis and tumor chemosensitivity, thus facilitating better 4.0/). Genes 2021, 12, 318. https://doi.org/10.3390/genes12020318 https://www.mdpi.com/journal/genes Genes 2021, 12, 318 2 of 21 patient stratification and identification of the patients requiring aggressive treatment strate- gies [9]. This review gives an overview of kidney development followed by a summary of how collecting duct and nephron progenitors contribute to normal renal morphogenesis in Genes 2021, 12, x FOR PEER REVIEW 2 of 22 order to better facilitate the understanding of their fundamental similarities and differences with Wilms tumor biology. FigureFigure 1. Nephroblastomatosis 1. Nephroblastomatosis and and Wilms Wilms tumor. tumor. ( (AA)) An example ofof humanhuman postnatal postnatal kidney kidney with with nephrogenic nephrogenic rests rests (asterisks)(asterisks) of the of the nephroblastomatosis, nephroblastomatosis, which which areare seenseen as as tightly tightly packed packed darker darker blue blue cells cells in the in renalthe renal cortex. cortex. (B) An (B example) An exam- ple of human kidney kidney with with the the classical classical morphology morphology of Wilms of Wilms tumor. tumor. It resembles It resembles embryonic embryonic kidney by kidney exhibiting by exhibiti blastemalng (Bblaste-), malstromal (B), stromal (S), and (S) epithelial, and epithelial cells (arrows), cells (arrows), which, however, which, however fail to organize, fail to into organize typical into tissue typical structures. tissue structures. 2. WilmsNephrons Tumor—the functional filtration units of mammalian kidneys—and renal stroma are derivedWilms from tumors metanephric (Figure1) are mesenchyme one of the most containing common soliddistinct tumors progenitor in children pool withs for an both lineagesincidence [5,6] of. 1:10,000,Metanephric usually tissue appearing is normally before lost the before age of five.birth Although in humans good but treatmentremains part ofoptions the undifferentiated exist for some histologicalnephrogenic tumor rests typesin Wilms and theirtumor survival patients rates [7,8] are. Understanding good, other thetypes, differences like anaplastic between Wilms normal tumors, tissue still-residing have a progenitors 5-year survival and of cancer only 50%.-causing Therefore, stem cells is thererequired remains to set a clear the stage clinical for need better for thecharacterization improvement of of Wilms transformations tumor therapeutic that turn options; normal kidneyto achieve progenitors this, a better into basicWilms understanding tumor stem cells of these. This tumors may essentially is essential. help with predicting individualizedAs reviewed disease extensively prognosis elsewhere and tumor [7], Wilms chemosensitivity tumors have been, thus intriguing facilitating clinicians, better pa- tientpathologists, stratification and and cancer identification geneticists forof th ae long patients time. requiring The tumors aggressive are the direct treatmen resultt strate- of giesproblems [9]. This during review the gives embryonic an overview development of kidney of the development kidney, and followed it was one by of a the summary cancer of types based on which Alfred Knudson developed his two-hit model for tumor suppressor how collecting duct and nephron progenitors contribute to normal renal morphogenesis genes [10]. It is widely believed that nephrogenic rests—embryonic tissues that are retained in order to better facilitate the understanding of their fundamental similarities and differ- in the postnatal kidney—are the precursor lesions of Wilms tumors, and indeed, the tumors encesthemselves with Wilms contain tumor cell typesbiology normally. found only in the embryonic kidney. A subset of cases, the ones caused by the loss of the Wilms Tumor1 (WT1) tumor suppressor gene, 2. additionallyWilms Tumor present with the development of ectopic, non-renal tissues, especially striated muscle. All this points to the disruption of normal development as the primary cause of WilmsWilms tumors. tumors We therefore(Figure 1) need are toone understand of the most normal common kidney solid development tumors in inchildren order to with anreally incidence understand of 1:10 Wilms,000, tumorsusually and appearing exploit this before understanding the age of to five. develop Although better and good more treat- mentspecific options therapies. exist Atfor the some same histological time, the primary tumor defect types leading and their to Wilms survival tumors rates could are begood, otherconsidered types, like a naturally anaplastic occurring Wilms model tumors, to understand still have a normal 5-year kidneysurvival development. of only 50%. There- fore, there remains a clear clinical need for the improvement of Wilms tumor therapeutic options3. Embryonic; to achieve Kidney this, a better basic understanding of these tumors is essential. AsKidney reviewed morphogenesis extensively is elsewhere a classic example [7], Wilms of balanced tumors have reciprocal been tissue intriguing interac- clini- cians,tions pathologists [11–13]. Much, and of ourcancer basic genet understandingicists for a oflong how time. the kidneyThe tumors develops are derivesthe direct from result the classical in vitro tissue recombination/induction experiments in different model organ- of problems during the embryonic development of the kidney, and it was one of the cancer isms that are complemented with in vivo gene inactivation studies
Load more

Recommended publications
  • Lncrnas in Non-Small-Cell Lung Cancer
    non-coding RNA Review LncRNAs in Non-Small-Cell Lung Cancer Lucy Ginn , Lei Shi, Manuela La Montagna and Michela Garofalo * Transcriptional Networks in Lung Cancer Group, Cancer Research UK Manchester Institute, University of Manchester, Alderley Park, Manchester SK10 4TG, UK; [email protected] (L.G.); [email protected] (L.S.); [email protected] (M.L.M.) * Correspondence: [email protected]; Tel.: +44-(0)-161-306-6056 Received: 27 May 2020; Accepted: 28 June 2020; Published: 30 June 2020 Abstract: Lung cancer is associated with a high mortality, with around 1.8 million deaths worldwide in 2018. Non-small-cell lung cancer (NSCLC) accounts for around 85% of cases and, despite improvement in the management of NSCLC, most patients are diagnosed at advanced stage and the five-year survival remains around 15%. This highlights a need to identify novel ways to treat the disease to reduce the burden of NSCLC. Long non-coding RNAs (lncRNAs) are non-coding RNA molecules longer than 200 nucleotides in length which play important roles in gene expression and signaling pathways. Recently, lncRNAs were implicated in cancer, where their expression is dysregulated resulting in aberrant functions. LncRNAs were shown to function as both tumor suppressors and oncogenes in a variety of cancer types. Although there are a few well characterized lncRNAs in NSCLC, many lncRNAs remain un-characterized and their mechanisms of action largely unknown. LncRNAs have success as therapies in neurodegenerative diseases, and having a detailed understanding of their function in NSCLC may guide novel therapeutic approaches and strategies.
    [Show full text]
  • Homeobox Gene Expression Profile in Human Hematopoietic Multipotent
    Leukemia (2003) 17, 1157–1163 & 2003 Nature Publishing Group All rights reserved 0887-6924/03 $25.00 www.nature.com/leu Homeobox gene expression profile in human hematopoietic multipotent stem cells and T-cell progenitors: implications for human T-cell development T Taghon1, K Thys1, M De Smedt1, F Weerkamp2, FJT Staal2, J Plum1 and G Leclercq1 1Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, Ghent, Belgium; and 2Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands Class I homeobox (HOX) genes comprise a large family of implicated in this transformation proces.14 The HOX-C locus transcription factors that have been implicated in normal and has been primarily implicated in lymphomas.15 malignant hematopoiesis. However, data on their expression or function during T-cell development is limited. Using degener- Hematopoietic cells are derived from stem cells that reside in ated RT-PCR and Affymetrix microarray analysis, we analyzed fetal liver (FL) in the embryo and in the adult bone marrow the expression pattern of this gene family in human multipotent (ABM), which have the unique ability to self-renew and thereby stem cells from fetal liver (FL) and adult bone marrow (ABM), provide a life-long supply of blood cells. T lymphocytes are a and in T-cell progenitors from child thymus. We show that FL specific type of hematopoietic cells that play a major role in the and ABM stem cells are similar in terms of HOX gene immune system. They develop through a well-defined order of expression, but significant differences were observed between differentiation steps in the thymus.16 Several transcription these two cell types and child thymocytes.
    [Show full text]
  • Functional Genomics Atlas of Synovial Fibroblasts Defining Rheumatoid Arthritis
    medRxiv preprint doi: https://doi.org/10.1101/2020.12.16.20248230; this version posted December 18, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Functional genomics atlas of synovial fibroblasts defining rheumatoid arthritis heritability Xiangyu Ge1*, Mojca Frank-Bertoncelj2*, Kerstin Klein2, Amanda Mcgovern1, Tadeja Kuret2,3, Miranda Houtman2, Blaž Burja2,3, Raphael Micheroli2, Miriam Marks4, Andrew Filer5,6, Christopher D. Buckley5,6,7, Gisela Orozco1, Oliver Distler2, Andrew P Morris1, Paul Martin1, Stephen Eyre1* & Caroline Ospelt2*,# 1Versus Arthritis Centre for Genetics and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK 2Department of Rheumatology, Center of Experimental Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland 3Department of Rheumatology, University Medical Centre, Ljubljana, Slovenia 4Schulthess Klinik, Zurich, Switzerland 5Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK 6NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK 7Kennedy Institute of Rheumatology, University of Oxford Roosevelt Drive Headington Oxford UK *These authors contributed equally #corresponding author: [email protected] NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. 1 medRxiv preprint doi: https://doi.org/10.1101/2020.12.16.20248230; this version posted December 18, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
    [Show full text]
  • 1714 Gene Comprehensive Cancer Panel Enriched for Clinically Actionable Genes with Additional Biologically Relevant Genes 400-500X Average Coverage on Tumor
    xO GENE PANEL 1714 gene comprehensive cancer panel enriched for clinically actionable genes with additional biologically relevant genes 400-500x average coverage on tumor Genes A-C Genes D-F Genes G-I Genes J-L AATK ATAD2B BTG1 CDH7 CREM DACH1 EPHA1 FES G6PC3 HGF IL18RAP JADE1 LMO1 ABCA1 ATF1 BTG2 CDK1 CRHR1 DACH2 EPHA2 FEV G6PD HIF1A IL1R1 JAK1 LMO2 ABCB1 ATM BTG3 CDK10 CRK DAXX EPHA3 FGF1 GAB1 HIF1AN IL1R2 JAK2 LMO7 ABCB11 ATR BTK CDK11A CRKL DBH EPHA4 FGF10 GAB2 HIST1H1E IL1RAP JAK3 LMTK2 ABCB4 ATRX BTRC CDK11B CRLF2 DCC EPHA5 FGF11 GABPA HIST1H3B IL20RA JARID2 LMTK3 ABCC1 AURKA BUB1 CDK12 CRTC1 DCUN1D1 EPHA6 FGF12 GALNT12 HIST1H4E IL20RB JAZF1 LPHN2 ABCC2 AURKB BUB1B CDK13 CRTC2 DCUN1D2 EPHA7 FGF13 GATA1 HLA-A IL21R JMJD1C LPHN3 ABCG1 AURKC BUB3 CDK14 CRTC3 DDB2 EPHA8 FGF14 GATA2 HLA-B IL22RA1 JMJD4 LPP ABCG2 AXIN1 C11orf30 CDK15 CSF1 DDIT3 EPHB1 FGF16 GATA3 HLF IL22RA2 JMJD6 LRP1B ABI1 AXIN2 CACNA1C CDK16 CSF1R DDR1 EPHB2 FGF17 GATA5 HLTF IL23R JMJD7 LRP5 ABL1 AXL CACNA1S CDK17 CSF2RA DDR2 EPHB3 FGF18 GATA6 HMGA1 IL2RA JMJD8 LRP6 ABL2 B2M CACNB2 CDK18 CSF2RB DDX3X EPHB4 FGF19 GDNF HMGA2 IL2RB JUN LRRK2 ACE BABAM1 CADM2 CDK19 CSF3R DDX5 EPHB6 FGF2 GFI1 HMGCR IL2RG JUNB LSM1 ACSL6 BACH1 CALR CDK2 CSK DDX6 EPOR FGF20 GFI1B HNF1A IL3 JUND LTK ACTA2 BACH2 CAMTA1 CDK20 CSNK1D DEK ERBB2 FGF21 GFRA4 HNF1B IL3RA JUP LYL1 ACTC1 BAG4 CAPRIN2 CDK3 CSNK1E DHFR ERBB3 FGF22 GGCX HNRNPA3 IL4R KAT2A LYN ACVR1 BAI3 CARD10 CDK4 CTCF DHH ERBB4 FGF23 GHR HOXA10 IL5RA KAT2B LZTR1 ACVR1B BAP1 CARD11 CDK5 CTCFL DIAPH1 ERCC1 FGF3 GID4 HOXA11 IL6R KAT5 ACVR2A
    [Show full text]
  • DNA Methylation Profiling Identifies the HOXA11 Gene As an Early Diagnostic and Prognostic Molecular Marker in Human Lung Adenocarcinoma
    www.impactjournals.com/oncotarget/ Oncotarget, 2017, Vol. 8, (No. 20), pp: 33100-33109 Research Paper DNA methylation profiling identifies the HOXA11 gene as an early diagnostic and prognostic molecular marker in human lung adenocarcinoma Qun Li1,2,*, Chang Chen3, Xiaohui Ren1, Weihong Sun1,* 1Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, 200031, China 2The State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China 3Department of Orthodontics, The First Affiliated Hospital of Zhengzhou University, Stomatological College Zhengzhou University, Zhengzhou, 450052, China *These authors contributed equally to this work Correspondence to: Weihong Sun, email: [email protected] Keywords: HOXA11, hypermethylation, lung adenocarcinoma, adenocarcinoma in situ, prognosis Received: October 11, 2016 Accepted: March 14, 2017 Published: March 23, 2017 Copyright: Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT DNA hypermethylation plays important roles in carcinogenesis by silencing key genes. The goal of our study was to identify pivotal genes using MethyLight and assessed their diagnostic and prognostic values in lung adenocarcinoma (AD). In the present study, we detected DNA methylation at sixteen loci promoter regions in twenty one pairs of primary human lung AD tissues and adjacent non-tumor lung (AdjNL) tissues using the real-time PCR (RT-PCR)-based method MethyLight.
    [Show full text]
  • HOXA10 Controls Osteoblastogenesis by Directly Activating Bone Regulatory and Phenotypic Genes
    University of Massachusetts Medical School eScholarship@UMMS Open Access Articles Open Access Publications by UMMS Authors 2007-02-28 HOXA10 controls osteoblastogenesis by directly activating bone regulatory and phenotypic genes Mohammad Q. Hassan University of Massachusetts Medical School Et al. Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/oapubs Part of the Life Sciences Commons, and the Medicine and Health Sciences Commons Repository Citation Hassan MQ, Tare RS, Lee SH, Mandeville M, Weiner B, Montecino MA, Van Wijnen AJ, Stein JL, Stein GS, Lian JB. (2007). HOXA10 controls osteoblastogenesis by directly activating bone regulatory and phenotypic genes. Open Access Articles. https://doi.org/10.1128/MCB.01544-06. Retrieved from https://escholarship.umassmed.edu/oapubs/1334 This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in Open Access Articles by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. MOLECULAR AND CELLULAR BIOLOGY, May 2007, p. 3337–3352 Vol. 27, No. 9 0270-7306/07/$08.00ϩ0 doi:10.1128/MCB.01544-06 Copyright © 2007, American Society for Microbiology. All Rights Reserved. HOXA10 Controls Osteoblastogenesis by Directly Activating Bone Regulatory and Phenotypic Genesᰔ Mohammad Q. Hassan,1 Rahul Tare,1† Suk Hee Lee,1 Matthew Mandeville,1 Brian Weiner,1 Martin Montecino,2 Andre J. van Wijnen,1 Janet L. Stein,1 Gary S. Stein,1 and Jane B. Lian1* Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01655,1 and Departamento de Bioquimica y Biologia Molecular, Facultad de Ciencias Biologicas, Universidad de Concepcion, Concepcion, Chile2 Received 18 August 2006/Returned for modification 4 October 2006/Accepted 9 February 2007 HOXA10 is necessary for embryonic patterning of skeletal elements, but its function in bone formation beyond this early developmental stage is unknown.
    [Show full text]
  • Genome-Wide Screening in Human Kidney Organoids Identifies Novel Aspects of Nephrogenesis
    bioRxiv preprint doi: https://doi.org/10.1101/2021.05.26.445745; this version posted May 27, 2021. 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. Genome-wide screening in human kidney organoids identifies novel aspects of nephrogenesis Rosemarie Ungricht1, Laure Guibbal1, Marie-Christine Lasbennes1, Vanessa Orsini1, Martin Beibel1, Annick Waldt1, Rachel Cuttat1, Walter Carbone1, Anne Basler1, Guglielmo Roma1, Florian Nigsch1, Jan Tchorz1, Dominic Hoepfner1, Philipp S. Hoppe1,2 1Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH-4056 Basel, Switzerland 2Lead contact *Correspondence: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.05.26.445745; this version posted May 27, 2021. 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 Human organoids allow studying proliferation, lineage specification, and three-dimensional tissue development. Due to the inherent multicellular complexity, interrogation by systematic genetic methodologies is challenging. Here, we present the first genome-wide CRISPR screen in iPSC-derived kidney organoids. The combination of genome editing, longitudinal sampling and sorting of specific cell populations enabled us to uncover novel biology from development to tubular morphogenesis. We validated the high quality of our screen by individual hit follow up and comparisons to kidney disease datasets. The discovery of a novel regulatory mechanism which controls epithelial proliferation via a trans-activating but cis-inhibitory effect of the Notch ligand Jagged1 proves how mosaic knockouts generated by pooled CRISPR screening in organoids can identify novel ways of communication between heterogeneous cell populations in complex tissues.
    [Show full text]
  • Three-Dimensional Regulation of HOXA Cluster Genes by a Cis-Element in Hematopoietic Stem Cell and Leukemia
    bioRxiv preprint doi: https://doi.org/10.1101/2020.04.16.017533; this version posted April 18, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Three-dimensional regulation of HOXA cluster genes by a cis-element in hematopoietic stem cell and leukemia. Xue Qing David Wang1, Haley Gore1, Pamela Himadewi1, Fan Feng2, Lu Yang3, Wanding Zhou1,5, Yushuai Liu1, Xinyu Wang4, Chun-wei Chen3, Jianzhong Su4, Jie Liu2, Gerd Pfeifer1,*, Xiaotian Zhang1,* 1. Center for Epigenetics, Van Andel Research Institute, Grand Rapids, Michigan 2. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan. 3. Department of System Biology, City of Hope Cancer Center, California 4. Institute of Biomedical Big Data, Wenzhou Medical University, Wenzhou, China 5. Current address: Children Hospital of Philadelphia, University of Pennsylvania *. These authors jointly supervise this project Correspondence should be addressed to Xiaotian Zhang: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/2020.04.16.017533; this version posted April 18, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Abstract: Proper gene regulation is crucial for cellular differentiation, and dysregulation of key genes can lead to diseased states such as cancer. The HOX transcription factors play such a role during hematopoiesis, and aberrant expression of certain HOXA genes is found in certain acute myeloid leukemias (AMLs).
    [Show full text]
  • Xo PANEL DNA GENE LIST
    xO PANEL DNA GENE LIST ~1700 gene comprehensive cancer panel enriched for clinically actionable genes with additional biologically relevant genes (at 400 -500x average coverage on tumor) Genes A-C Genes D-F Genes G-I Genes J-L AATK ATAD2B BTG1 CDH7 CREM DACH1 EPHA1 FES G6PC3 HGF IL18RAP JADE1 LMO1 ABCA1 ATF1 BTG2 CDK1 CRHR1 DACH2 EPHA2 FEV G6PD HIF1A IL1R1 JAK1 LMO2 ABCB1 ATM BTG3 CDK10 CRK DAXX EPHA3 FGF1 GAB1 HIF1AN IL1R2 JAK2 LMO7 ABCB11 ATR BTK CDK11A CRKL DBH EPHA4 FGF10 GAB2 HIST1H1E IL1RAP JAK3 LMTK2 ABCB4 ATRX BTRC CDK11B CRLF2 DCC EPHA5 FGF11 GABPA HIST1H3B IL20RA JARID2 LMTK3 ABCC1 AURKA BUB1 CDK12 CRTC1 DCUN1D1 EPHA6 FGF12 GALNT12 HIST1H4E IL20RB JAZF1 LPHN2 ABCC2 AURKB BUB1B CDK13 CRTC2 DCUN1D2 EPHA7 FGF13 GATA1 HLA-A IL21R JMJD1C LPHN3 ABCG1 AURKC BUB3 CDK14 CRTC3 DDB2 EPHA8 FGF14 GATA2 HLA-B IL22RA1 JMJD4 LPP ABCG2 AXIN1 C11orf30 CDK15 CSF1 DDIT3 EPHB1 FGF16 GATA3 HLF IL22RA2 JMJD6 LRP1B ABI1 AXIN2 CACNA1C CDK16 CSF1R DDR1 EPHB2 FGF17 GATA5 HLTF IL23R JMJD7 LRP5 ABL1 AXL CACNA1S CDK17 CSF2RA DDR2 EPHB3 FGF18 GATA6 HMGA1 IL2RA JMJD8 LRP6 ABL2 B2M CACNB2 CDK18 CSF2RB DDX3X EPHB4 FGF19 GDNF HMGA2 IL2RB JUN LRRK2 ACE BABAM1 CADM2 CDK19 CSF3R DDX5 EPHB6 FGF2 GFI1 HMGCR IL2RG JUNB LSM1 ACSL6 BACH1 CALR CDK2 CSK DDX6 EPOR FGF20 GFI1B HNF1A IL3 JUND LTK ACTA2 BACH2 CAMTA1 CDK20 CSNK1D DEK ERBB2 FGF21 GFRA4 HNF1B IL3RA JUP LYL1 ACTC1 BAG4 CAPRIN2 CDK3 CSNK1E DHFR ERBB3 FGF22 GGCX HNRNPA3 IL4R KAT2A LYN ACVR1 BAI3 CARD10 CDK4 CTCF DHH ERBB4 FGF23 GHR HOXA10 IL5RA KAT2B LZTR1 ACVR1B BAP1 CARD11 CDK5 CTCFL DIAPH1 ERCC1 FGF3 GID4 HOXA11
    [Show full text]
  • Long Non-Coding RNA HOXA11 Antisense Promotes Cell Proliferation and Invasion and Predicts Patient Prognosis in Serous Ovarian Cancer
    pISSN 1598-2998, eISSN 2005-9256 Cancer Res Treat. 2017;49(3):656-668 https://doi.org/10.4143/crt.2016.263 Original Article Open Access Long Non-coding RNA HOXA11 Antisense Promotes Cell Proliferation and Invasion and Predicts Patient Prognosis in Serous Ovarian Cancer Ga Won Yim, MD, PhD1,2 Purpose Hee Jung Kim, PhD3 The biological function of long non-coding RNAs (lncRNAs) is only partially understood; there- fore, in this study, we investigated the expression of the novel HOXA11 antisense Lee Kyung Kim, MS3 (HOXA11as) lncRNA and its oncogenic role in serous ovarian cancer (SOC). Sang Wun Kim, MD, PhD3 Sunghoon Kim, MD, PhD3 Materials and Methods Eun Ji Nam, MD, PhD3 HOXA11as expression was examined in 129 SOC tissue samples by real time reverse tran- Young Tae Kim, MD, PhD3 scription polymerase chain reaction. Clinicopathological factors and patient survival were compared between the high (n=27) and low HOXA11as expression group (n=102). To investigate the role of HOXA11as in cell proliferation, invasion, and migration, HOXA11as expression in ovarian cancer cells was knocked down using RNA interference. 1 Department of Obstetrics and Gynecology, Results National Medical Center, Seoul, HOXA11as expression in cancer tissue was 77-fold higher than that of noncancerous tissue 2Department of Obstetrics and Gynecology, Yonsei University Graduate School, Seoul, (p < 0.05). Higher HOXA11as expression was significantly correlated with histological grade 3Department of Obstetrics and Gynecology, (p=0.017) and preoperative cancer antigen 125 (p=0.048). HOXA11as overexpression in Institute of Women's Life Medical Science, SOC cells led to increased cell proliferation, invasion, and migration.
    [Show full text]
  • BMC Biology Biomed Central
    BMC Biology BioMed Central Research article Open Access Classification and nomenclature of all human homeobox genes PeterWHHolland*†1, H Anne F Booth†1 and Elspeth A Bruford2 Address: 1Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, UK and 2HUGO Gene Nomenclature Committee, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK Email: Peter WH Holland* - [email protected]; H Anne F Booth - [email protected]; Elspeth A Bruford - [email protected] * Corresponding author †Equal contributors Published: 26 October 2007 Received: 30 March 2007 Accepted: 26 October 2007 BMC Biology 2007, 5:47 doi:10.1186/1741-7007-5-47 This article is available from: http://www.biomedcentral.com/1741-7007/5/47 © 2007 Holland 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: The homeobox genes are a large and diverse group of genes, many of which play important roles in the embryonic development of animals. Increasingly, homeobox genes are being compared between genomes in an attempt to understand the evolution of animal development. Despite their importance, the full diversity of human homeobox genes has not previously been described. Results: We have identified all homeobox genes and pseudogenes in the euchromatic regions of the human genome, finding many unannotated, incorrectly annotated, unnamed, misnamed or misclassified genes and pseudogenes.
    [Show full text]
  • Supplementary File Table S1
    Supplementary file Table S1 Grouping of Homeobox genes according to their main known function. Anatomical Structure Morphogenesis EN1, HOXC10, HOXC13, HOXD3, LBX1, SIX2, SIX4 Organ Morphogenesis CDX1, CDX2, HOXA11, HOXA13, ISL1, LHX1, PAX3, PDHX, PITX2, PITX3, PROX1, SIX6 Body Pattern Formation ALX3, EMX2, HHEX, HOXA11, HOXA2, HOXA4, HOXA5, HOXA6, HOXB1, HOXB5, HOXB6, HOXC5, HOXD10, HOXD8, LMX1B, PITX2 Ectoderm Development PROX1, VAX2 Endoderm Development HOXC11 Brain & Nervous System Development Brain Development ALX1, DLX2, EMX2 Nervous System Development: ARX, DLX5, DLX6, HOXD10, LBX1, LHX1, OTP, PAX3, PHOX2A, PHOX2B Skeletal Development: ALX3, ALX4, DLX3, DLX5, DLX6, EN1, HOXA11, HOXA13, HOXA2, HOXB6, HOXD10, HOXD13, MSX2 Muscle Development: BARX2, MKX, SIRT1, SIRT2, SIX1 Other Homeobox Genes Involved In BARX1, CDX4, CUX1, DLX1, EMX1, EN2, Multicellular Organismal HOXA1, HOXA7, HOXA9, HOXB13, HOXB2, Development: HOXB3, HOXB4, HOXB7, HOXB8, HOXB9, HOXC12, HOXC8, HOXC9, HOXD1, HOXD11, HOXD12, HOXD9, ISL2, LBX2, LMX1A, MEIS1, NKX3-1, OTX1, TLX1, VAX1, VSX1, VSX2 Homeobox Genes Involved In Cell ARX, EMX2, HHEX, HLX, HOPX, LBX1, LHX1, Differentiation: LMX1B, MIXL1, OTP, PHOX2A, SIRT1, VSX2 Other Genes: PHTF1, SIRT3, SIRT6, SIRT7, ZHX1, ZHX2 Homeobox genes include two subsets of genes coding for transcription factors involved in multiple functions. The clustered HOX genes are indicated in bold. Supplementary file Figure S2 5’ Spatial collinearity 3’ HOXA Chr. 7p15.3 HOXB Chr. 17q21.3 HOXC Chr. 12q13.3 HOXD Chr. 2q31 13 12 11 10 9 8 7 6 5 4 3 2 1 Paralogous HOX groups Distribution of the 39 human HOX genes in four clusters located in different chromosomal regions*. Blue indicates anterior HOX genes. Yellow, paralogy group 3 Hox genes, green and purple indicatete central HOX genes and Red the posterior HOX genes.
    [Show full text]