DOCSLIB.ORG

Supplementary Tables Table S1. List of the 121 Lung Cancer Cell Lines

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Supplementary Tables Table S1. List of the 121 lung cancer cell lines screened for MAX alterations. Information about the histopathology of each cell line, and the presence of alterations at MYC and BRG1 is also included. Grey boxes indicate that no information is available. Table S2. List of genes that are up-regulated or down-regulated upon MAX reconstitution. The values represent the n-fold change in the level of gene expression of each of the lung cancer cell lines infected with the wild type MAX relative to the controls (Ø). Table S3. List of genes that are up-regulated or down-regulated upon depletion of BRG1. The values represent the n-fold change in the level of gene expression of each of the lung cancer cell lines infected with the shBRG1 relative to the controls Ø. Table S4. List of the cell lines included in Figure 5. The information about alterations at the indicated genes was obtained from different sources, as indicated. For data extracted from databases we applied the following criteria to define a mutation: i) mutations at tumor suppressor genes (BRG1, SMARCB1, MAX, ARID1A, PRBM1, and MGA) should be homozygous and predictive of truncated proteins, ii) for amplification at the MYC family of oncogenes, only very high levels of gene amplification have been considered to be positive. Other genes, related to MYC/MAX or to the SWI/SNF complex, have also been searched for alterations (i.e., ARID1B, ARID2, MXI, MXDs) but either no alterations were reported in the databases or the changes did not fulfill our selection criteria. CCLE, Cancer Cell Line Encyclopedia (Broad-Novartis Cancer Cell Line Encyclopedia; website, http://www.broadinstitute.org/ccle/). COSMIC, Catalogue of Somatic Mutations in Cancer (Trust Sanger Institute’s Cancer Cell Line Project; website, http://cancer.sanger.ac.uk/). Table S1: List of the 121 lung cancer cell lines screened for MAX alterations. Information about the histopathology of each cell line, and the presence of alterations at MYC and BRG1 is also included. Grey boxes indicate that no information is available. Cell line Histopathology MAX BRG1 MYC MYCL1 MYCN H1417 SCLC Mutant LU134 SCLC Mutant LU165 SCLC Mutant CORL95 SCLC Mutant A427 AC Mutant A549 AC Mutant DMS114 SCLC Mutant H1299 LCC/NSCLC Mutant H1573 AC Mutant H1703 AC Mutant H1819 AC Mutant H2126 AC Mutant H23 AC Mutant HCC366 AC Mutant H522 AC Mutant H661 LCC Mutant H841 SCLC Mutant HCC15 SCC Mutant Ma29 AC Mutant RERFLCMS AC Mutant DMS273 SCLC Ampl. Ampl. H1395 AC Ampl. H187 SCLC Ampl. H1975 AC Ampl. H2122 AC Ampl. H2170 SCC Ampl. H2171 SCLC Ampl. H446 SCLC Ampl. H460 AC Ampl. H524 SCLC Ampl. H82 SCLC Ampl. HCC44 AC Ampl. Lu135 SCLC Ampl. LU65 LCC/NSCLC Ampl. N417 SCLC Ampl. H1963 SCLC Ampl. H2029 SCLC Ampl. H2107 SCLC Ampl. H2141 SCLC Ampl. H510 SCLC Ampl. H889 SCLC Ampl. HCC33 SCLC Ampl. H1770 Neuroendocrine Ampl. H526 SCLC Ampl. H69 SCLC Ampl. H720 CARCINOID Ampl. ABC1 AC CALU1 SCC CALU3 AC DMS153 SCLC DMS53 SCLC EBC1 SCC H1048 AC H1155 LCC/NSCLC H1184 SCLC H128 SCLC H1339 SCLC H1385 NSCLC H1436 SCLC H1437 AC H1450 SCLC H1607 SCLC H1618 SCLC H1623 AC H1648 AC H1650 AC H1672 SCLC H1930 SCLC AC H1993 H2009 AC H2081 SCLC H2087 AC H209 SCLC H2195 SCLC H2196 SCLC H2227 SCLC H2291 AC H2347 AC H249 SCLC H322 AC H345 SCLC H441 AC H520 SCC H596 AC-SCC H711 SCLC H719 SCLC H727 LCC/NSCLC H774 SCLC H820 AC HCC193 AC HCC515 AC HCC78 AC HCC827 AC HCC95 SCC II-18 AC LC1SQSF SCC LK2 SCC Lu139 SCLC Lu24 SCLC LU99 LCC/NSCLC Ma1 AC Ma10 AC Ma12 AC Ma17 AC Ma2 LCC Ma24 AC Ma25 LCC Ma26 AC Ms18 SCLC PC10 SCC PC13 LCC PC14 AC PC3 AC PC7 AC PC9 AC RERF-LC-OK AC SBC5 SCLC SHP77 SCLC SKMES1 SCC MAX-signature Supplementary Table S2 OFFICIAL_GENGene Name Lu134_H1417_Lu165_MAX TNFSF12 TNFSF12-TNFSF13 readthrough transcript; tumor necrosis factor (ligand) superfamily, 1.123 1.424 5.376 KISS1R kinesin family member 20A 1.865 2.569 2.258 GDF15 growth differentiation factor 15 1.865 5.97 2.203 ADAD2 adenosine deaminase domain containing 2 1.156 1.477 2.058 MCTP2 multiple coagulation factor deficiency 2 1.282 1.354 2.056 NIM1 naked cuticle homolog 2 (Drosophila) 1.146 2.434 2.014 ADAMTS18 ADAM metallopeptidase with thrombospondin type 1 motif, 18 1.5 2.189 1.955 PRSS56 PRSS56 1.199 2.311 1.946 ENST000004404ENST00000440451 1.732 2.671 1.908 SSC5D hypothetical LOC284297 1.105 1.446 1.904 FAM162A family with sequence similarity 162, member A 1.63 2.047 1.856 APLN apelin 1.409 2.404 1.82 IER3 heparan sulfate proteoglycan 2 1.311 1.746 1.761 PRR7 proline rich 7 (synaptic) 1.081 1.123 1.75 HK2 histone cluster 1, H3j; histone cluster 1, H3i; histone cluster 1, H3h; histone cluster 1, H 3.783 7.459 1.746 SYCE3 synaptonemal complex central element protein 3 1.211 1.635 1.717 RCOR2 REST corepressor 2 1.119 1.685 1.716 BNIP3 BCL2/adenovirus E1B 19kDa interacting protein 3 2.105 2.326 1.714 C4orf47 chromosome 4 open reading frame 47 2.01 1.933 1.69 SV2B synaptic vesicle glycoprotein 2B; hypothetical protein LOC100128403 1.23 1.681 1.669 GMPR glutaminase 1.646 1.479 1.65 CXCR4 chemokine (C-X-C motif) receptor 4 1.357 2.051 1.646 SLC9B1 solute carrier family 9, subfamily B 1.095 1.232 1.644 C6orf57 chromosome 6 open reading frame 57 1.239 1.619 1.639 LOC728730 similar to hCG2031213 1.272 1.331 1.635 C7orf52 chromosome 7 open reading frame 52 1.36 2.152 1.633 NRTN neurotensin 1.133 1.715 1.626 VEGFA vascular endothelial growth factor A 7.84 4.103 1.61 KREMEN2 kallikrein-related peptidase 11 1.112 1.628 1.604 DDIT3 DNA-damage-inducible transcript 3 1.208 2.248 1.603 ADA adenosine deaminase 2.06 3.379 1.595 PFKFB3 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 1.503 2.912 1.583 F12 coagulation factor XII (Hageman factor) 1.235 1.426 1.583 LOC285141 hypothetical protein LOC283713 1.385 1.717 1.582 Page 1 MAX-signature P4HA1 prolyl 4-hydroxylase, alpha polypeptide I 1.989 2.651 1.581 STC2 stanniocalcin 2 1.938 1.506 1.58 COPZ2 coatomer protein complex, subunit zeta 2 1.148 2.314 1.578 MLKL MHC class I polypeptide-related sequence B 1.339 1.499 1.578 VWA5A von Willebrand factor A domain containing 5A 1.291 2.354 1.575 TMEM130 transmembrane protein 130 1.101 1.744 1.566 SNORD114-23 small nucleolar RNA, C/D box 114-14; small nucleolar RNA, C/D box 113-1; small nucle 1.134 1.376 1.564 WFDC2 WAP four-disulfide core domain 2 1.45 1.329 1.562 ABCG4 ATP-binding cassette, sub-family G (WHITE), member 4 1.116 1.714 1.561 MMP10 matrix metallopeptidase 1 (interstitial collagenase) 2.266 1.317 1.55 ADM adrenomedullin 1.893 2.329 1.537 FUT3 fucosyltransferase 3 (galactoside 3(4)-L-fucosyltransferase, Lewis blood group) 1.171 3.059 1.534 GPR172B G protein-coupled receptor 171 1.126 1.566 1.525 LOC100289187 similar to Protein FAM27D1 1.376 1.743 1.524 GAL3ST1 galactose-3-O-sulfotransferase 1 1.07 1.537 1.519 TRIB3 tribbles homolog 3 (Drosophila) 2.903 4.329 1.511 BATF2 basic leucine zipper transcription factor, ATF-like 2 1.295 2.269 1.505 FBXO2 F-box protein 2 1.151 2.177 1.505 AHNAK AHNAK nucleoprotein 1.392 1.199 1.504 ESRP1 epithelial splicing regulatory protein 1 1.237 1.713 1.502 MMP1 MLX interacting protein-like 1.503 1.247 1.501 NGEF neuronal guanine nucleotide exchange factor 0.947 2.059 1.496 PARP14 poly (ADP-ribose) polymerase family, member 14 1.109 4.825 1.494 FHOD1 formin homology 2 domain containing 1 1.104 2.194 1.493 LOC155060 hypothetical protein LOC149351 1.236 1.431 1.489 SEC24D SEC24 family, member D (S. cerevisiae) 1.155 1.257 1.488 TMC4 transmembrane channel-like 4 1.456 1.923 1.486 SYNGR3 synaptogyrin 3 1.112 1.959 1.485 TXNIP thioredoxin interacting protein 1.51 1.839 1.485 NFATC4 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4 1.383 2.132 1.483 RELB v-rel reticuloendotheliosis viral oncogene homolog B 1.249 1.412 1.48 PFKFB4 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 1.494 3.673 1.48 C1orf213 chromosome 1 open reading frame 213 1.115 1.477 1.475 PLA2G4D phospholipase A2, group IVD (cytosolic) 1.106 2.561 1.472 FGF11 fibroblast growth factor 11 1.275 1.546 1.472 SLC16A3 solute carrier family 16, member 3 (monocarboxylic acid transporter 4) 5.221 4.071 1.468 Page 2 MAX-signature MYO15A v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian) 1.599 2.224 1.467 APOE hypothetical LOC100129500; apolipoprotein E 1.549 5.763 1.466 MSMB mannose-P-dolichol utilization defect 1 1.95 1.26 1.461 AATK apoptosis-associated tyrosine kinase 2.453 2.297 1.461 SMPDL3A sphingomyelin phosphodiesterase, acid-like 3A 1.916 1.336 1.46 PDK1 pyruvate dehydrogenase kinase, isozyme 1 1.904 4.317 1.458 GRTP1 gastrin-releasing peptide 1.245 1.876 1.453 ATF3 activating transcription factor 3 1.389 1.43 1.448 ROPN1 ropporin, rhophilin associated protein 1 2.063 1.728 1.446 LDHA leucine carboxyl methyltransferase 2 2.049 1.97 1.446 MOXD1 matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) 1.269 1.632 1.444 ZNF204P zinc finger protein 204 pseudogene 1.374 1.582 1.441 ATP1B2 ATPase, Na+/K+ transporting, beta 2 polypeptide 1.411 2.633 1.438 OBFC1 obscurin-like 1 1.12 1.401 1.436 SERPINA6 serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 6 1.194 1.802 1.436 RPRML reprimo-like 1.133 2.012 1.434 LOC100507401 LOC100507401 1.135 1.66 1.431 BIK BCL2-interacting killer (apoptosis-inducing) 1.866 1.478 1.431 FLJ37644 hypothetical gene supported by AK094963 1.17 1.365 1.428 EML2 echinoderm microtubule associated protein like 2 1.954 1.773 1.428 TMEM45B transmembrane protein 45B 2.067 1.403 1.425 PLOD2 procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 1.513 1.727 1.424 CLDN1
Recommended publications
  • A Genetic Screening Identifies a Component of the SWI/SNF Complex, Arid1b As a Senescence Regulator

    A Genetic Screening Identifies a Component of the SWI/SNF Complex, Arid1b As a Senescence Regulator

    A genetic screening identifies a component of the SWI/SNF complex, Arid1b as a senescence regulator Sadaf Khan A thesis submitted to Imperial College London for the degree of Doctor in Philosophy MRC Clinical Sciences Centre Imperial College London, School of Medicine July 2013 Statement of originality All experiments included in this thesis were performed by myself unless otherwise stated. Copyright Declaration The copyright of this thesis rests with the author and is made available under a Creative Commons Attribution Non-Commercial No Derivatives license. Researchers are free to copy, distribute or transmit the thesis on the condition that they attribute it, that they do not use it for commercial purposes and that they do not alter, transform or build upon it. For any reuse or redistribution, researchers must make clear to others the license terms of this work. 2 Abstract Senescence is an important tumour suppressor mechanism, which prevents the proliferation of stressed or damaged cells. The use of RNA interference to identify genes with a role in senescence is an important tool in the discovery of novel cancer genes. In this work, a protocol was established for conducting bypass of senescence screenings, using shRNA libraries together with next-generation sequencing. Using this approach, the SWI/SNF subunit Arid1b was identified as a regulator of cellular lifespan in MEFs. SWI/SNF is a large multi-subunit complex that remodels chromatin. Mutations in SWI/SNF proteins are frequently associated with cancer, suggesting that SWI/SNF components are tumour suppressors. Here the role of ARID1B during senescence was investigated. Depletion of ARID1B extends the proliferative capacity of primary mouse and human fibroblasts.
  • Connexin 40.1 (GJD4) (NM 153368) Human Tagged ORF Clone Lentiviral Particle – RC222438L3V | Origene

    Connexin 40.1 (GJD4) (NM 153368) Human Tagged ORF Clone Lentiviral Particle – RC222438L3V | Origene

    OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for RC222438L3V Connexin 40.1 (GJD4) (NM_153368) Human Tagged ORF Clone Lentiviral Particle Product data: Product Type: Lentiviral Particles Product Name: Connexin 40.1 (GJD4) (NM_153368) Human Tagged ORF Clone Lentiviral Particle Symbol: GJD4 Synonyms: CX40.1 Vector: pLenti-C-Myc-DDK-P2A-Puro (PS100092) ACCN: NM_153368 ORF Size: 1110 bp ORF Nucleotide The ORF insert of this clone is exactly the same as(RC222438). Sequence: OTI Disclaimer: The molecular sequence of this clone aligns with the gene accession number as a point of reference only. However, individual transcript sequences of the same gene can differ through naturally occurring variations (e.g. polymorphisms), each with its own valid existence. This clone is substantially in agreement with the reference, but a complete review of all prevailing variants is recommended prior to use. More info OTI Annotation: This clone was engineered to express the complete ORF with an expression tag. Expression varies depending on the nature of the gene. RefSeq: NM_153368.1 RefSeq Size: 1580 bp RefSeq ORF: 1113 bp Locus ID: 219770 UniProt ID: Q96KN9 Protein Families: Transmembrane MW: 40 kDa Gene Summary: Connexins, such as GJD4, are involved in the formation of gap junctions, intercellular conduits that directly connect the cytoplasms of contacting cells. Each gap junction channel is formed by docking of 2 hemichannels, each of which contains 6 connexin subunits (Sohl et al., 2003 [PubMed 12881038]).[supplied by OMIM, Mar 2008] This product is to be used for laboratory only.
  • Podocyte Specific Knockdown of Klf15 in Podocin-Cre Klf15flox/Flox Mice Was Confirmed

    Podocyte Specific Knockdown of Klf15 in Podocin-Cre Klf15flox/Flox Mice Was Confirmed

    SUPPLEMENTARY FIGURE LEGENDS Supplementary Figure 1: Podocyte specific knockdown of Klf15 in Podocin-Cre Klf15flox/flox mice was confirmed. (A) Primary glomerular epithelial cells (PGECs) were isolated from 12-week old Podocin-Cre Klf15flox/flox and Podocin-Cre Klf15+/+ mice and cultured at 37°C for 1 week. Real-time PCR was performed for Nephrin, Podocin, Synaptopodin, and Wt1 mRNA expression (n=6, ***p<0.001, Mann-Whitney test). (B) Real- time PCR was performed for Klf15 mRNA expression (n=6, *p<0.05, Mann-Whitney test). (C) Protein was also extracted and western blot analysis for Klf15 was performed. The representative blot of three independent experiments is shown in the top panel. The bottom panel shows the quantification of Klf15 by densitometry (n=3, *p<0.05, Mann-Whitney test). (D) Immunofluorescence staining for Klf15 and Wt1 was performed in 12-week old Podocin-Cre Klf15flox/flox and Podocin-Cre Klf15+/+ mice. Representative images from four mice in each group are shown in the left panel (X 20). Arrows show colocalization of Klf15 and Wt1. Arrowheads show a lack of colocalization. Asterisk demonstrates nonspecific Wt1 staining. “R” represents autofluorescence from RBCs. In the right panel, a total of 30 glomeruli were selected in each mouse and quantification of Klf15 staining in the podocytes was determined by the ratio of Klf15+ and Wt1+ cells to Wt1+ cells (n=6 mice, **p<0.01, unpaired t test). Supplementary Figure 2: LPS treated Podocin-Cre Klf15flox/flox mice exhibit a lack of recovery in proteinaceous casts and tubular dilatation after DEX administration.
  • Further Delineation of Chromosomal Consensus Regions in Primary

    Further Delineation of Chromosomal Consensus Regions in Primary

    Leukemia (2007) 21, 2463–2469 & 2007 Nature Publishing Group All rights reserved 0887-6924/07 $30.00 www.nature.com/leu ORIGINAL ARTICLE Further delineation of chromosomal consensus regions in primary mediastinal B-cell lymphomas: an analysis of 37 tumor samples using high-resolution genomic profiling (array-CGH) S Wessendorf1,6, TFE Barth2,6, A Viardot1, A Mueller3, HA Kestler3, H Kohlhammer1, P Lichter4, M Bentz5,HDo¨hner1,PMo¨ller2 and C Schwaenen1 1Klinik fu¨r Innere Medizin III, Zentrum fu¨r Innere Medizin der Universita¨t Ulm, Ulm, Germany; 2Institut fu¨r Pathologie, Universita¨t Ulm, Ulm, Germany; 3Forschungsdozentur Bioinformatik, Universita¨t Ulm, Ulm, Germany; 4Abt. Molekulare Genetik, Deutsches Krebsforschungszentrum, Heidelberg, Germany and 5Sta¨dtisches Klinikum Karlsruhe, Karlsruhe, Germany Primary mediastinal B-cell lymphoma (PMBL) is an aggressive the expression of BSAP, BOB1, OCT2, PAX5 and PU1 was extranodal B-cell non-Hodgkin’s lymphoma with specific clin- added to the spectrum typical of PMBL features.9 ical, histopathological and genomic features. To characterize Genetically, a pattern of highly recurrent karyotype alterations further the genotype of PMBL, we analyzed 37 tumor samples and PMBL cell lines Med-B1 and Karpas1106P using array- with the hallmark of chromosomal gains of the subtelomeric based comparative genomic hybridization (matrix- or array- region of chromosome 9 supported the concept of a unique CGH) to a 2.8k genomic microarray. Due to a higher genomic disease entity that distinguishes PMBL from other B-cell non- resolution, we identified altered chromosomal regions in much Hodgkin’s lymphomas.10,11 Together with less specific gains on higher frequencies compared with standard CGH: for example, 2p15 and frequent mutations of the SOCS1 gene, a notable þ 9p24 (68%), þ 2p15 (51%), þ 7q22 (32%), þ 9q34 (32%), genomic similarity to classical Hodgkin’s lymphoma was þ 11q23 (18%), þ 12q (30%) and þ 18q21 (24%).
  • Ankrd9 Is a Metabolically-Controlled Regulator of Impdh2 Abundance and Macro-Assembly

    Ankrd9 Is a Metabolically-Controlled Regulator of Impdh2 Abundance and Macro-Assembly

    ANKRD9 IS A METABOLICALLY-CONTROLLED REGULATOR OF IMPDH2 ABUNDANCE AND MACRO-ASSEMBLY by Dawn Hayward A dissertation submitted to The Johns Hopkins University in conformity with the requirements of the degree of Doctor of Philosophy Baltimore, Maryland April 2019 ABSTRACT Members of a large family of Ankyrin Repeat Domains proteins (ANKRD) regulate numerous cellular processes by binding and changing properties of specific protein targets. We show that interactions with a target protein and the functional outcomes can be markedly altered by cells’ metabolic state. ANKRD9 facilitates degradation of inosine monophosphate dehydrogenase 2 (IMPDH2), the rate-limiting enzyme in GTP biosynthesis. Under basal conditions ANKRD9 is largely segregated from the cytosolic IMPDH2 by binding to vesicles. Upon nutrient limitation, ANKRD9 loses association with vesicles and assembles with IMPDH2 into rod-like structures, in which IMPDH2 is stable. Inhibition of IMPDH2 with Ribavirin favors ANKRD9 binding to rods. The IMPDH2/ANKRD9 assembly is reversed by guanosine, which restores association of ANKRD9 with vesicles. The conserved Cys109Cys110 motif in ANKRD9 is required for the vesicles-to-rods transition as well as binding and regulation of IMPDH2. ANKRD9 knockdown increases IMPDH2 levels and prevents formation of IMPDH2 rods upon nutrient limitation. Thus, the status of guanosine pools affects the mode of ANKRD9 action towards IMPDH2. Advisor: Dr. Svetlana Lutsenko, Department of Physiology, Johns Hopkins University School of Medicine Second reader:
  • ARID1B Is a Specific Vulnerability in ARID1A-Mutant Cancers The

    ARID1B Is a Specific Vulnerability in ARID1A-Mutant Cancers The

    ARID1B is a specific vulnerability in ARID1A-mutant cancers The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters. Citation Helming, K. C., X. Wang, B. G. Wilson, F. Vazquez, J. R. Haswell, H. E. Manchester, Y. Kim, et al. 2014. “ARID1B is a specific vulnerability in ARID1A-mutant cancers.” Nature medicine 20 (3): 251-254. doi:10.1038/nm.3480. http://dx.doi.org/10.1038/nm.3480. Published Version doi:10.1038/nm.3480 Accessed February 16, 2015 10:04:32 PM EST Citable Link http://nrs.harvard.edu/urn-3:HUL.InstRepos:12987227 Terms of Use This article was downloaded from Harvard University's DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA (Article begins on next page) NIH Public Access Author Manuscript Nat Med. Author manuscript; available in PMC 2014 September 01. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Nat Med. 2014 March ; 20(3): 251–254. doi:10.1038/nm.3480. ARID1B is a specific vulnerability in ARID1A-mutant cancers Katherine C. Helming1,2,3,4,*, Xiaofeng Wang1,2,3,*, Boris G. Wilson1,2,3, Francisca Vazquez5, Jeffrey R. Haswell1,2,3, Haley E. Manchester1,2,3, Youngha Kim1,2,3, Gregory V. Kryukov5, Mahmoud Ghandi5, Andrew J. Aguirre5,6,7, Zainab Jagani8, Zhong Wang9, Levi A. Garraway6, William C. Hahn6,7, and Charles W.
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus

    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.
  • Protein Identities in Evs Isolated from U87-MG GBM Cells As Determined by NG LC-MS/MS

    Protein Identities in Evs Isolated from U87-MG GBM Cells As Determined by NG LC-MS/MS

    Protein identities in EVs isolated from U87-MG GBM cells as determined by NG LC-MS/MS. No. Accession Description Σ Coverage Σ# Proteins Σ# Unique Peptides Σ# Peptides Σ# PSMs # AAs MW [kDa] calc. pI 1 A8MS94 Putative golgin subfamily A member 2-like protein 5 OS=Homo sapiens PE=5 SV=2 - [GG2L5_HUMAN] 100 1 1 7 88 110 12,03704523 5,681152344 2 P60660 Myosin light polypeptide 6 OS=Homo sapiens GN=MYL6 PE=1 SV=2 - [MYL6_HUMAN] 100 3 5 17 173 151 16,91913397 4,652832031 3 Q6ZYL4 General transcription factor IIH subunit 5 OS=Homo sapiens GN=GTF2H5 PE=1 SV=1 - [TF2H5_HUMAN] 98,59 1 1 4 13 71 8,048185945 4,652832031 4 P60709 Actin, cytoplasmic 1 OS=Homo sapiens GN=ACTB PE=1 SV=1 - [ACTB_HUMAN] 97,6 5 5 35 917 375 41,70973209 5,478027344 5 P13489 Ribonuclease inhibitor OS=Homo sapiens GN=RNH1 PE=1 SV=2 - [RINI_HUMAN] 96,75 1 12 37 173 461 49,94108966 4,817871094 6 P09382 Galectin-1 OS=Homo sapiens GN=LGALS1 PE=1 SV=2 - [LEG1_HUMAN] 96,3 1 7 14 283 135 14,70620005 5,503417969 7 P60174 Triosephosphate isomerase OS=Homo sapiens GN=TPI1 PE=1 SV=3 - [TPIS_HUMAN] 95,1 3 16 25 375 286 30,77169764 5,922363281 8 P04406 Glyceraldehyde-3-phosphate dehydrogenase OS=Homo sapiens GN=GAPDH PE=1 SV=3 - [G3P_HUMAN] 94,63 2 13 31 509 335 36,03039959 8,455566406 9 Q15185 Prostaglandin E synthase 3 OS=Homo sapiens GN=PTGES3 PE=1 SV=1 - [TEBP_HUMAN] 93,13 1 5 12 74 160 18,68541938 4,538574219 10 P09417 Dihydropteridine reductase OS=Homo sapiens GN=QDPR PE=1 SV=2 - [DHPR_HUMAN] 93,03 1 1 17 69 244 25,77302971 7,371582031 11 P01911 HLA class II histocompatibility antigen,
  • Transcriptomic Analysis of Native Versus Cultured Human and Mouse Dorsal Root Ganglia Focused on Pharmacological Targets Short

    Transcriptomic Analysis of Native Versus Cultured Human and Mouse Dorsal Root Ganglia Focused on Pharmacological Targets Short

    bioRxiv preprint doi: https://doi.org/10.1101/766865; this version posted September 12, 2019. 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-ND 4.0 International license. Transcriptomic analysis of native versus cultured human and mouse dorsal root ganglia focused on pharmacological targets Short title: Comparative transcriptomics of acutely dissected versus cultured DRGs Andi Wangzhou1, Lisa A. McIlvried2, Candler Paige1, Paulino Barragan-Iglesias1, Carolyn A. Guzman1, Gregory Dussor1, Pradipta R. Ray1,#, Robert W. Gereau IV2, # and Theodore J. Price1, # 1The University of Texas at Dallas, School of Behavioral and Brain Sciences and Center for Advanced Pain Studies, 800 W Campbell Rd. Richardson, TX, 75080, USA 2Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine # corresponding authors [email protected], [email protected] and [email protected] Funding: NIH grants T32DA007261 (LM); NS065926 and NS102161 (TJP); NS106953 and NS042595 (RWG). The authors declare no conflicts of interest Author Contributions Conceived of the Project: PRR, RWG IV and TJP Performed Experiments: AW, LAM, CP, PB-I Supervised Experiments: GD, RWG IV, TJP Analyzed Data: AW, LAM, CP, CAG, PRR Supervised Bioinformatics Analysis: PRR Drew Figures: AW, PRR Wrote and Edited Manuscript: AW, LAM, CP, GD, PRR, RWG IV, TJP All authors approved the final version of the manuscript. 1 bioRxiv preprint doi: https://doi.org/10.1101/766865; this version posted September 12, 2019. 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.
  • Transcriptome Analysis of Gravitational Effects on Mouse Skeletal Muscles Under Microgravity and Artificial 1 G Onboard Environm

    Transcriptome Analysis of Gravitational Effects on Mouse Skeletal Muscles Under Microgravity and Artificial 1 G Onboard Environm

    www.nature.com/scientificreports OPEN Transcriptome analysis of gravitational efects on mouse skeletal muscles under microgravity and artifcial 1 g onboard environment Risa Okada1,2, Shin‑ichiro Fujita3,4, Riku Suzuki5,6, Takuto Hayashi3,5, Hirona Tsubouchi5, Chihiro Kato5,7, Shunya Sadaki5, Maho Kanai5,6, Sayaka Fuseya3,5, Yuri Inoue3,5, Hyojung Jeon5, Michito Hamada5, Akihiro Kuno5,6, Akiko Ishii8, Akira Tamaoka8, Jun Tanihata9, Naoki Ito10, Dai Shiba1,2, Masaki Shirakawa1,2, Masafumi Muratani1,4, Takashi Kudo1,5* & Satoru Takahashi1,5* Spacefight causes a decrease in skeletal muscle mass and strength. We set two murine experimental groups in orbit for 35 days aboard the International Space Station, under artifcial earth‑gravity (artifcial 1 g; AG) and microgravity (μg; MG), to investigate whether artifcial 1 g exposure prevents muscle atrophy at the molecular level. Our main fndings indicated that AG onboard environment prevented changes under microgravity in soleus muscle not only in muscle mass and fber type composition but also in the alteration of gene expression profles. In particular, transcriptome analysis suggested that AG condition could prevent the alterations of some atrophy‑related genes. We further screened novel candidate genes to reveal the muscle atrophy mechanism from these gene expression profles. We suggest the potential role of Cacng1 in the atrophy of myotubes using in vitro and in vivo gene transductions. This critical project may accelerate the elucidation of muscle atrophy mechanisms. Gravity is the most constant factor afecting the entire process of evolution of organisms on Earth. As adapting to a changing environment is key for any organism’s survival, the constant mechanical stimulus of gravitational force has been shared by all organisms on Earth through evolution 1.
  • Figure S1. Representative Report Generated by the Ion Torrent System Server for Each of the KCC71 Panel Analysis and Pcafusion Analysis

    Figure S1. Representative Report Generated by the Ion Torrent System Server for Each of the KCC71 Panel Analysis and Pcafusion Analysis

    Figure S1. Representative report generated by the Ion Torrent system server for each of the KCC71 panel analysis and PCaFusion analysis. (A) Details of the run summary report followed by the alignment summary report for the KCC71 panel analysis sequencing. (B) Details of the run summary report for the PCaFusion panel analysis. A Figure S1. Continued. Representative report generated by the Ion Torrent system server for each of the KCC71 panel analysis and PCaFusion analysis. (A) Details of the run summary report followed by the alignment summary report for the KCC71 panel analysis sequencing. (B) Details of the run summary report for the PCaFusion panel analysis. B Figure S2. Comparative analysis of the variant frequency found by the KCC71 panel and calculated from publicly available cBioPortal datasets. For each of the 71 genes in the KCC71 panel, the frequency of variants was calculated as the variant number found in the examined cases. Datasets marked with different colors and sample numbers of prostate cancer are presented in the upper right. *Significantly high in the present study. Figure S3. Seven subnetworks extracted from each of seven public prostate cancer gene networks in TCNG (Table SVI). Blue dots represent genes that include initial seed genes (parent nodes), and parent‑child and child‑grandchild genes in the network. Graphical representation of node‑to‑node associations and subnetwork structures that differed among and were unique to each of the seven subnetworks. TCNG, The Cancer Network Galaxy. Figure S4. REVIGO tree map showing the predicted biological processes of prostate cancer in the Japanese. Each rectangle represents a biological function in terms of a Gene Ontology (GO) term, with the size adjusted to represent the P‑value of the GO term in the underlying GO term database.
  • Repeat Proteins Challenge the Concept of Structural Domains

    Repeat Proteins Challenge the Concept of Structural Domains

    844 Biochemical Society Transactions (2015) Volume 43, part 5 Repeat proteins challenge the concept of structural domains Rocıo´ Espada*1, R. Gonzalo Parra*1, Manfred J. Sippl†, Thierry Mora‡, Aleksandra M. Walczak§ and Diego U. Ferreiro*2 *Protein Physiology Lab, Dep de Qu´ımica Biologica, ´ Facultad de Ciencias Exactas y Naturales, UBA-CONICET-IQUIBICEN, Buenos Aires, C1430EGA, Argentina †Center of Applied Molecular Engineering, Division of Bioinformatics, Department of Molecular Biology, University of Salzburg, 5020 Salzburg, Austria ‡Laboratoire de physique statistique, CNRS, UPMC and Ecole normale superieure, ´ 24 rue Lhomond, 75005 Paris, France §Laboratoire de physique theorique, ´ CNRS, UPMC and Ecole normale superieure, ´ 24 rue Lhomond, 75005 Paris, France Abstract Structural domains are believed to be modules within proteins that can fold and function independently. Some proteins show tandem repetitions of apparent modular structure that do not fold independently, but rather co-operate in stabilizing structural forms that comprise several repeat-units. For many natural repeat-proteins, it has been shown that weak energetic links between repeats lead to the breakdown of co-operativity and the appearance of folding sub-domains within an apparently regular repeat array. The quasi-1D architecture of repeat-proteins is crucial in detailing how the local energetic balances can modulate the folding dynamics of these proteins, which can be related to the physiological behaviour of these ubiquitous biological systems. Introduction and between repeats, challenging the concept of structural It was early on noted that many natural proteins typically domain. collapse stretches of amino acid chains into compact units, defining structural domains [1]. These domains typically correlate with biological activities and many modern proteins can be described as composed by novel ‘domain arrange- Definition of the repeat-units ments’ [2].