DOCSLIB.ORG

Homeobox Gene Expression Profile in Human Hematopoietic Multipotent

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read 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. As the most 17–21 immature thymocytes are derived from immigrated FL and factors have a crucial role in this developmental process, 22 ABM stem cells, this indicates a drastic change in HOX gene resulting in a complex regulatory network. Little is known, expression upon entry into the thymus. Further analysis of however, if HOX genes also play a role during T-cell HOX-A7, HOX-A9, HOX-A10, and HOX-A11 expression with development. A crucial role for HOX-A9 in this developmental specific RT-PCR in all thymocyte differentiation stages showed process was elucidated by the generation of HOX-A9À/À mice.23 a sequential loss of 30 region HOX-A cluster genes during Thymocytes from these animals are blocked at an early stage of intrathymic T-cell development and an unexpected expression 24 of HOX-A11, previously not recognized to play a role in differentiation. Other evidence for the role of HOX genes in hematopoiesis. Also HOX-B3 and HOX-C4 were expressed thymopoiesis came from a study in which enforced expression throughout thymocyte development. Overall, these data pro- of HOX-B3 resulted in skewing of T-cell progenitors towards the vide novel evidence for an important role of certain HOX genes gd T-cell lineage instead of the ab-lineage.25 in human T-cell development. Human CD34+ lineage-marker negative (LinÀ) FL stem cells Leukemia (2003) 17, 1157–1163. doi:10.1038/sj.leu.2402947 26 Keywords: HOX; T-cell development; human; transcription factors have been shown previously to generate T cells, while in contrast, ABM stem cells seem to have a strongly diminished capacity to generate these cells.27,28 In this study, we therefore compared the expression pattern of HOX genes between highly purified CD34+LinÀ cells from both sources to investigate if Introduction differences in HOX gene expression are present that can account for the difference in T-cell differentiation potential. In Class I homeobox (HOX) genes code for transcription factors addition, to have a better insight in which genes might be that are characterized by a highly conserved region of 60 amino involved in T-cell development, we also analyzed HOX gene acids that is responsible for DNA binding.1 Generally, this gene expression in the earliest multipotent progenitor cells in the human thymus and in the earliest T-cell committed progenitor family is divided into two different classes. Class I HOX genes 29 were discovered in Drosophila because of the appearance of the cells. We show that in terms of HOX gene expression, virtually so-called ‘homeotic mutations’, mutations that cause transfor- no difference could be detected between FL and ABM stem mation of one part of the body into another.2 In the genome of cells, but that important differences in the expression pattern of vertebrates, they are arranged in four different gene clusters and this gene family were apparent between thymic and nonthymic share a high degree of homology. In man, 39 HOX members precursor cells. Furthermore, specific RT-PCR reactions for have been identified so far.3 Class II homeobox genes are the selected genes showed an intriguing expression profile for HOX- divergent homeobox genes. These genes have less homology. A cluster genes during human thymocyte development and Originally identified as master regulatory genes during expression of HOX-B3 and HOX-C4 throughout this develop- embryogenesis, research over the last decade has provided mental pathway. ample evidence to postulate that the HOX gene family is also able to control proliferation and differentiation of hematopoietic cells.4–6 Various reports have indicated the involvement of HOX Materials and methods genes in leukemogenesis, underlining their role in normal hematopoiesis. Several HOX genes are involved in the Monoclonal antibodies transformation of hematopoietic cells as a result of translocation events, especially with NUP98, a nucleoporin gene.7–10 Mouse anti-human MoAbs used were CD1a (OKT6 fluorescein Furthermore, high-level expression of both HOX-A9 and HOX- isothiocyanate (FITC)), CD3 (OKT3 FITC), CD4 (OKT4 FITC), A10 is frequently detected in leukemic blasts from patients with CD7 (3A1 FITC), CD8a (OKT8 FITC) and CD19 (Leu12) from acute myeloid leukemia,11–13 and also HOX-B6 was recently American Type Culture Collection (ATCC, Rockville, MD, USA); CD3 (Leu-4 phycoerythrin (PE) or allophycocyanine (APC)), Correspondence: Dr G Leclercq, Ghent University Hospital, 4BlokA, CD4 (Leu-3a PE or APC), CD34 (HPCA-2 FITC, PE or APC) and De Pintelaan 185, Ghent B-9000, Belgium. Fax: +32 9 2403 659 CD69 (L78 PE) from Becton Dickinson Immunocytometry Received 11 September 2002; accepted 14 February 2003 Systems (BDIS, Mountain View, CA, USA); CD1a (T6 PE) and HOX gene expression in T-cell progenitors T Taghon et al 1158 TCR panab (BMA031 PE) from Coulter (Miami, FL, USA); immunomagnetic depletion was performed with unlabeled glycophorin-A (10F7MN) and CD8b (2ST8.5H7 unlabeled or CD8b antibody, and subsequently, cells were stained with FITC), a kind gift of Dr L Lanier (DNAX, Palo Alto, CA, USA) and CD8a-FITC, rat anti-mouse-IgG2a+b-PE (which detects the Dr E Reinherz (Dana-Farber Cancer Institute, Boston, MA, USA), unlabeled CD8b antibody) and CD3-APC to sort + À À + respectively. Rat anti-mouse-IgG2a+b (X57 PE) from BDIS was CD8a CD8b CD3 cells. All these cells are CD4 . For used to detect the unlabeled CD8b antibody. purification of CD4+CD8ab+CD3À, CD4+CD8ab+CD3+CD69À and CD4+CD8ab+CD3+CD69+ cells, thymocytes were labeled with CD8b-FITC, CD69-PE and CD4-APC. The Cell sources CD8b+CD69+CD4+ fraction contains only CD3+ cells and therefore represents the CD4+CD8ab+CD3+CD69+ cells, while FL tissues were obtained after legal termination of pregnancy, the CD8b+CD69ÀCD4+ fraction contains both the ABM was collected from healthy donors, and child thymus (CT) CD4+CD8ab+CD3À and CD4+CD8ab+CD3+CD69À popula- was obtained from children undergoing cardiac surgery. All tions. Therefore, sorted CD8b+CD69ÀCD4+ cells were labeled human tissues were obtained with informed consent and used with CD3-PE to allow subsequent sorting of both fractions. For according to the guidelines of the Medical Ethical Commission sorting of TCRab+CD4+CD8À and TCRab+CD8+CD4À cells, of the University Hospital Ghent. FL cells were isolated by thymocytes were labeled with CD8a-FITC, TCRab-PE and CD4- gentle disruption of the tissue in complete medium (Iscove’s APC. Cells were sorted on a FACS Vantage (BDIS) using modified Dulbecco’s medium/10% fetal calf serum (FCS), all CellQuest software (BDIS) and checked for purity, which was from Invitrogen, Carlsbad, CA, USA). Child thymocytes were always at least 98.5%. obtained by cutting the thymic tissue into small pieces of 0.5 cm  0.5 cm, which were then extensively teased apart with cataract knives in serum-free RPMI 1640 medium (Invitrogen). RNA isolation, RT-PCR, cloning of PCR products and Mononuclear cells from all tissues were obtained by density- sequence analysis gradient centrifugation over Lymphoprep (Nyegaard, Oslo, Norway) and were subsequently resuspended in 9 vol FCS RNA from purified progenitor cells and different thymocyte (Invitrogen) and 1 vol dimethyl sulfoxide (Serva, Heidelberg, subsets was isolated using Trizol (Invitrogen) according to the Germany), and cryopreserved in liquid N2 until use. instructions of the supplier, treated with DNAseI (Promega Coorporation, Madison, WI, USA) to avoid genomic DNA contamination, and cDNA was prepared using Superscript Purification of hematopoietic precursor cells and (Invitrogen) following the guidelines of the manufacturer. HOX thymocyte subsets homeodomain degenerated primers used for amplification were modified at the 50-end by providing restriction sites that were not After thawing and washing the cells, cells were labeled with present in any of the 39 homeodomains, to facilitate subsequent lineage-specific antibodies and precursor cells from all human cloning into the pUC18 plasmid (Invitrogen). A BamHI site was tissues were enriched by immunomagnetic depletion of Lin+ included in the forward primer: 50-GCGGATCCGA(AG)(TC)TI- cells (using sheep anti-mouse Ig-coated Dynabeads (Dynal AS, GA(AG)AA(AG)GA(AG)TT(CT)C(AT)IT(AT)(CT)A-30 and a Hin- Oslo, Norway) with a ratio cells/Dynabeads of 1/5), followed by dIII site in the reverse primer: 50-GCGAAGCTT(AG)(CT)IC(GT)- cell sorting.
Load more

Recommended publications
  • Original Article Upregulation of HOXA13 As a Potential Tumorigenesis and Progression Promoter of LUSC Based on Qrt-PCR and Bioinformatics
    Int J Clin Exp Pathol 2017;10(10):10650-10665 www.ijcep.com /ISSN:1936-2625/IJCEP0065149 Original Article Upregulation of HOXA13 as a potential tumorigenesis and progression promoter of LUSC based on qRT-PCR and bioinformatics Rui Zhang1*, Yun Deng1*, Yu Zhang1, Gao-Qiang Zhai1, Rong-Quan He2, Xiao-Hua Hu2, Dan-Ming Wei1, Zhen-Bo Feng1, Gang Chen1 Departments of 1Pathology, 2Medical Oncology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China. *Equal contributors. Received September 7, 2017; Accepted September 29, 2017; Epub October 1, 2017; Published October 15, 2017 Abstract: In this study, we investigated the levels of homeobox A13 (HOXA13) and the mechanisms underlying the co-expressed genes of HOXA13 in lung squamous cancer (LUSC), the signaling pathways in which the co-ex- pressed genes of HOXA13 are involved and their functional roles in LUSC. The clinical significance of 23 paired LUSC tissues and adjacent non-tumor tissues were gathered. HOXA13 levels in LUSC were detected by quantita- tive real-time polymerase chain reaction (qRT-PCR). HOXA13 levels in LUSC from The Cancer Genome Atlas (TCGA) and Oncomine were analyzed. We performed receiver operator characteristic (ROC) curves of various clinicopath- ological features of LUSC. Co-expressed of HOXA13 were collected from MEM, cBioPortal and GEPIA. The func- tions and pathways of the most reliable overlapped genes were achieved from the Gene Otology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively. The protein-protein interaction (PPI) net- works were mapped using STRING. HOXA13 in LUSC were markedly upregulated compared with those in the non- cancerous controls as demonstrated by qRT-PCR (LUSC: 0.330±0.360; CONTROLS: 0.155±0.142; P=0.021).
    [Show full text]
  • HOXC4 Rabbit Pab
    Leader in Biomolecular Solutions for Life Science HOXC4 Rabbit pAb Catalog No.: A13856 Basic Information Background Catalog No. This gene belongs to the homeobox family of genes. The homeobox genes encode a A13856 highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox Observed MW gene clusters, HOXA, HOXB, HOXC and HOXD, which are located on different 30kDa chromosomes and consist of 9 to 11 genes arranged in tandem. This gene, HOXC4, is one of several homeobox HOXC genes located in a cluster on chromosome 12. Three Calculated MW genes, HOXC5, HOXC4 and HOXC6, share a 5' non-coding exon. Transcripts may include 29kDa the shared exon spliced to the gene-specific exons, or they may include only the gene- specific exons. Two alternatively spliced variants that encode the same protein have Category been described for HOXC4. Transcript variant one includes the shared exon, and transcript variant two includes only gene-specific exons. Primary antibody Applications WB Cross-Reactivity Mouse, Rat Recommended Dilutions Immunogen Information WB 1:500 - 1:2000 Gene ID Swiss Prot 3221 P09017 Immunogen Recombinant fusion protein containing a sequence corresponding to amino acids 30-130 of human HOXC4 (NP_055435.2). Synonyms HOXC4;HOX3;HOX3E;cp19 Contact Product Information www.abclonal.com Source Isotype Purification Rabbit IgG Affinity purification Storage Store at -20℃. Avoid freeze / thaw cycles. Buffer: PBS with 0.02% sodium azide,50% glycerol,pH7.3. Validation Data Western blot analysis of extracts of various cell lines, using HOXC4 antibody (A13856) at 1:3000 dilution.
    [Show full text]
  • Role of Hox Genes in Regulating Digit Patterning ROCÍO PÉREZ-GÓMEZ, ENDIKA HARO, MARC FERNÁNDEZ-GUERRERO, MARÍA F
    Int. J. Dev. Biol. 62: 797-805 (2018) https://doi.org/10.1387/ijdb.180200mr www.intjdevbiol.com Role of Hox genes in regulating digit patterning ROCÍO PÉREZ-GÓMEZ, ENDIKA HARO, MARC FERNÁNDEZ-GUERRERO, MARÍA F. BASTIDA and MARÍA A. ROS* Instituto de Biomedicina y Biotecnología de Cantabria, CSIC–SODERCAN Universidad de Cantabria, Santander, Spain ABSTRACT The distal part of the tetrapod limb, the autopod, is characterized by the presence of digits. The digits display a wide diversity of shapes and number reflecting selection pressure for functional adaptation. Despite extensive study, the different aspects of digit patterning, as well as the factors and mechanisms involved are not completely understood. Here, we review the evidence implicating Hox proteins in digit patterning and the interaction between Hox genes and the Sonic hedgehog/Gli3 pathway, the other major regulator of digit number and identity. Currently, it is well accepted that a self-organizing Turing-type mechanism underlies digit patterning, this being understood as the establishment of an iterative arrangement of digit/interdigit in the hand plate. We also discuss the involvement of 5’ Hox genes in regulating digit spacing in the digital plate and therefore the number of digits formed in this self-organizing system. KEY WORDS: limb development, Hox gene, digit patterning, Shh, Gli3 Introduction and Meyer, 2015). The digits are crucial elements for the function of the limb. They The basic plan of the tetrapod limb includes three distinct can be viewed as serial identical structures arranged along the proximo-distal (PD) segments: the stylopod (arm), the zeugopod antero-posterior (AP) axis of the autopod, thumb to little finger, or (forearm) and the autopod (hand/foot).
    [Show full text]
  • KLF2 Induced
    UvA-DARE (Digital Academic Repository) The transcription factor KLF2 in vascular biology Boon, R.A. Publication date 2008 Link to publication Citation for published version (APA): Boon, R. A. (2008). The transcription factor KLF2 in vascular biology. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:23 Sep 2021 Supplementary data: Genes induced by KLF2 Dekker et al. LocusLink Accession Gene Sequence Description Fold p-value ID number symbol change (FDR) 6654 AK022099 SOS1 cDNA FLJ12037 fis, clone HEMBB1001921. 100.00 5.9E-09 56999 AF086069 ADAMTS9 full length insert cDNA clone YZ35C05. 100.00 1.2E-09 6672 AF085934 SP100 full length insert cDNA clone YR57D07. 100.00 6.7E-13 9031 AF132602 BAZ1B Williams Syndrome critical region WS25 mRNA, partial sequence.
    [Show full text]
  • 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.
    [Show full text]
  • Genetic Variability in the Italian Heavy Draught Horse from Pedigree Data and Genomic Information
    Supplementary material for manuscript: Genetic variability in the Italian Heavy Draught Horse from pedigree data and genomic information. Enrico Mancin†, Michela Ablondi†, Roberto Mantovani*, Giuseppe Pigozzi, Alberto Sabbioni and Cristina Sartori ** Correspondence: [email protected] † These two Authors equally contributed to the work Supplementary Figure S1. Mares and foal of Italian Heavy Draught Horse (IHDH; courtesy of Cinzia Stoppa) Supplementary Figure S2. Number of Equivalent Generations (EqGen; above) and pedigree completeness (PC; below) over years in Italian Heavy Draught Horse population. Supplementary Table S1. Descriptive statistics of homozygosity (observed: Ho_obs; expected: Ho_exp; total: Ho_tot) in 267 genotyped individuals of Italian Heavy Draught Horse based on the number of homozygous genotypes. Parameter Mean SD Min Max Ho_obs 35,630.3 500.7 34,291 38,013 Ho_exp 35,707.8 64.0 35,010 35,740 Ho_tot 50,674.5 93.8 49,638 50,714 1 Definitions of the methods for inbreeding are in the text. Supplementary Figure S3. Values of BIC obtained by analyzing values of K from 1 to 10, corresponding on the same amount of clusters defining the proportion of ancestry in the 267 genotyped individuals. Supplementary Table S2. Estimation of genomic effective population size (Ne) traced back to 18 generations ago (Gen. ago). The linkage disequilibrium estimation, adjusted for sampling bias was also included (LD_r2), as well as the relative standard deviation (SD(LD_r2)). Gen. ago Ne LD_r2 SD(LD_r2) 1 100 0.009 0.014 2 108 0.011 0.018 3 118 0.015 0.024 4 126 0.017 0.028 5 134 0.019 0.031 6 143 0.021 0.034 7 156 0.023 0.038 9 173 0.026 0.041 11 189 0.029 0.046 14 213 0.032 0.052 18 241 0.036 0.058 Supplementary Table S3.
    [Show full text]
  • Effect of Testosterone and Hypoxia on the Expansion of Umbilical Cord Blood CD34+ Cells in Vitro
    EXPERIMENTAL AND THERAPEUTIC MEDICINE 14: 4467-4475, 2017 Effect of testosterone and hypoxia on the expansion of umbilical cord blood CD34+ cells in vitro LIPING ZHOU1,2, XIAOWEI ZHANG2, PANPAN ZHOU1, XUE LI1, XUEJING XU1, QING SHI1, DONG LI1 and XIULI JU1 1Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, Shandong 250012; 2Department of Pediatrics, The Sixth People's Hospital of Jinan, Jinan, Shandong 250200, P.R. China Received October 12, 2016; Accepted June 15, 2017 DOI: 10.3892/etm.2017.5026 Abstract. Successfully expanding hematopoietic stem cells Therefore, the results of the current study indicate that a combina- (HSCs) is advantageous for clinical HSC transplantation. The tion of hypoxia and testosterone may be a promising cultivation present study investigated the influence of testosterone on the condition for HSC/hemopoietic progenitor cell expansion ex vivo. proliferation, antigen phenotype and expression of hemato- poiesis-related genes in umbilical cord blood-derived cluster Introduction of differentiation (CD)34+ cells under normoxic or hypoxia conditions. Cord blood (CB) CD34+ cells were separated using Hematopoietic stem cell (HSC) transplantation is a poten- magnetic activated cell sorting. A cytokine cocktail and feeder tially life-saving procedure used to treat a broad spectrum cells were used to stimulate the expansion of CD34+ cells under of disorders, including hematological, immune and genetic normoxic (20% O2) and hypoxic (1% O2) conditions for 7 days diseases (1). It has been demonstrated that bone marrow and testosterone was added accordingly. Cells were identified reconstituting HSCs reside within a small subpopulation using flow cytometry and reconstruction capacity was deter- of bone marrow or blood-derived mononuclear cells that mined using a colony-forming unit (CFU) assay.
    [Show full text]
  • 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]
  • HES1, Two Programs: Promoting the Quiescence and Proliferation of Adult Neural Stem Cells
    Downloaded from genesdev.cshlp.org on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press OUTLOOK HES1, two programs: promoting the quiescence and proliferation of adult neural stem cells Lachlan Harris and François Guillemot The Francis Crick Institute, London NW1 1AT, United Kingdom Adult neural stem cells are mostly quiescent and only bition of this pathway drives neuronal differentiation rarely enter the cell cycle to self-renew and generate neu- (Imayoshi et al. 2013). Specifically, they had determined ronal or glial progenies. The Notch signaling pathway is that Notch signaling induces proliferation via activating essential for both the quiescent and proliferative states the expression of the transcriptional repressor HES1, of neural stem cells. However, these are mutually exclu- whose protein levels oscillate due to autorepression (Hir- sive cellular states; thus, how Notch promotes both of ata et al. 2002). The oscillation of the HES1 protein then these programs within adult neural stem cells has re- induces the out of phase oscillation of its target gene, mained unclear. In this issue of Genes & Development, Achaete–scute homolog 1 (Ascl1), which in turn activates Sueda and colleagues (pp. 511–523) use an extensive reper- the transcription of positive regulators of cell cycle pro- toire of mouse genetic tools and techniques to demon- gression. Conversely, inhibition of the Notch pathway strate that it is the levels and dynamic expression of the down-regulates HES1 below a critical level, resulting in Notch transcriptional effector Hairy and Enhancer of sustained, rather than oscillatory, ASCL1 expression and Split 1 that enables this dual role. the induction of neuronal genes (Imayoshi et al.
    [Show full text]
  • Gabriel Dover)
    Dear Mr Darwin (Gabriel Dover) Home | Intro | About | Feedback | Prev | Next | Search Steele: Lamarck's Was Signature Darwin Wrong? Molecular Drive: the Third Force in evolution Geneticist Gabriel Dover claims that there is a third force in evolution: 'Molecular Drive' beside natural selection and neutral drift. Molecular drive is operationally distinct from natural selection and neutral drift. According to Dover it explains biological phenomena, such as the 700 copies of a ribosomal RNA gene and the origin of the 173 legs of the centipede, which natural selection and neutral drift alone cannot explain. by Gert Korthof version 1.3 24 Mar 2001 Were Darwin and Mendel both wrong? Molecular Drive is, according to Dover, an important factor in evolution, because it shapes the genomes and forms of organisms. Therefore Neo-Darwinism is incomplete without Molecular Drive. It is no wonder that the spread of novel genes was ascribed to natural selection, because it was the only known process that could promote the spread of novel genes. Dover doesn't reject the existence of natural selection but points out cases where natural selection clearly fails as a mechanism. Molecular drive is a non-Darwinian mechanism because it is independent of selection. We certainly need forces in evolution, since natural selection itself is not a force. It is the passive outcome of other processes. It is not an active process, notwithstanding its name. Natural selection as an explanation is too powerful for its own good. Molecular drive is non-Mendelian because some DNA segments are multiplied disproportional. In Mendelian genetics genes are present in just two copies (one on the maternal and one on the paternal chromosome).
    [Show full text]
  • Supplemental Materials ZNF281 Enhances Cardiac Reprogramming
    Supplemental Materials ZNF281 enhances cardiac reprogramming by modulating cardiac and inflammatory gene expression Huanyu Zhou, Maria Gabriela Morales, Hisayuki Hashimoto, Matthew E. Dickson, Kunhua Song, Wenduo Ye, Min S. Kim, Hanspeter Niederstrasser, Zhaoning Wang, Beibei Chen, Bruce A. Posner, Rhonda Bassel-Duby and Eric N. Olson Supplemental Table 1; related to Figure 1. Supplemental Table 2; related to Figure 1. Supplemental Table 3; related to the “quantitative mRNA measurement” in Materials and Methods section. Supplemental Table 4; related to the “ChIP-seq, gene ontology and pathway analysis” and “RNA-seq” and gene ontology analysis” in Materials and Methods section. Supplemental Figure S1; related to Figure 1. Supplemental Figure S2; related to Figure 2. Supplemental Figure S3; related to Figure 3. Supplemental Figure S4; related to Figure 4. Supplemental Figure S5; related to Figure 6. Supplemental Table S1. Genes included in human retroviral ORF cDNA library. Gene Gene Gene Gene Gene Gene Gene Gene Symbol Symbol Symbol Symbol Symbol Symbol Symbol Symbol AATF BMP8A CEBPE CTNNB1 ESR2 GDF3 HOXA5 IL17D ADIPOQ BRPF1 CEBPG CUX1 ESRRA GDF6 HOXA6 IL17F ADNP BRPF3 CERS1 CX3CL1 ETS1 GIN1 HOXA7 IL18 AEBP1 BUD31 CERS2 CXCL10 ETS2 GLIS3 HOXB1 IL19 AFF4 C17ORF77 CERS4 CXCL11 ETV3 GMEB1 HOXB13 IL1A AHR C1QTNF4 CFL2 CXCL12 ETV7 GPBP1 HOXB5 IL1B AIMP1 C21ORF66 CHIA CXCL13 FAM3B GPER HOXB6 IL1F3 ALS2CR8 CBFA2T2 CIR1 CXCL14 FAM3D GPI HOXB7 IL1F5 ALX1 CBFA2T3 CITED1 CXCL16 FASLG GREM1 HOXB9 IL1F6 ARGFX CBFB CITED2 CXCL3 FBLN1 GREM2 HOXC4 IL1F7
    [Show full text]
  • The Phylogeny of Squamate Reptiles (Lizards, Snakes, and Amphisbaenians) Inferred from Nine Nuclear Protein-Coding Genes
    C. R. Biologies 328 (2005) 1000–1008 http://france.elsevier.com/direct/CRASS3/ Evolution / Évolution The phylogeny of squamate reptiles (lizards, snakes, and amphisbaenians) inferred from nine nuclear protein-coding genes Nicolas Vidal a,b,∗, S. Blair Hedges a a Department of Biology and Astrobiology Research Center, 208 Mueller Lab., Pennsylvania State University, University Park, PA 16802-5301, USA b UMS 602, Taxonomie et collections, Reptiles–Amphibiens, département « Systématique et Évolution », Muséum national d’histoire naturelle, 25, rue Cuvier, Paris 75005, France Received 14 September 2005; accepted 3 October 2005 Available online 27 October 2005 Presented by Pierre Buser Abstract Squamate reptiles number approximately 8000 living species and are a major component of the world’s terrestrial vertebrate diversity. However, the established relationships of the higher-level groups have been questioned in recent molecular analyses. Here we expand the molecular data to include DNA sequences, totaling 6192 base pairs (bp), from nine nuclear protein-coding genes (C-mos, RAG1, RAG2, R35, HOXA13, JUN, α-enolase, amelogenin and MAFB) for 19 taxa representing all major lineages. Our phylogenetic analyses yield a largely resolved phylogeny that challenges previous morphological analyses and requires a new classification. The limbless dibamids are the most basal squamates. Of the remaining taxa (Bifurcata), the gekkonids form a basal lineage. The Unidentata, squamates that are neither dibamids nor gekkonids, are divided into the Scinciformata (scincids, xantusiids, and cordylids) and the Episquamata (remaining taxa). Episquamata includes Laterata (Teiformata, Lacertiformata, and Amphisbaenia, with the latter two joined in Lacertibaenia) and Toxicofera (iguanians, anguimorphs and snakes). Our results reject several previous hypotheses that identified either the varanids, or a burrowing lineage such as amphisbaenians or dibamids, as the closest relative of snakes.
    [Show full text]