DOCSLIB.ORG

Description Gene Symbol Refseq P -Value Fold Change Visual Perception Bestrophin 1 BEST1 NM 004183.2 4.07E-09 86.99 Retinal Pigm

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Description Gene Symbol Refseq P -Value Fold Change Visual Perception Bestrophin 1 BEST1 NM 004183.2 4.07E-09 86.99 Retinal Pigm Supplementary Table 1. Genes Significantly Upregulated in Expression in Retina Compared to FVMs Gene Fold Description RefSeq P -value Symbol change Visual perception Bestrophin 1 BEST1 NM_004183.2 4.07E-09 86.99 Retinal pigment epithelium-specific protein 65kDa RPE65 NM_000329.2 1.70E-10 86.03 Retinaldehyde binding protein 1 RLBP1 NM_000326.3 3.42E-07 84.89 Retinal G protein coupled receptor RGR NM_001012720.18.61E-09 55.26 Tyrosinase (oculocutaneous albinism IA) TYR NM_000372.4 1.94E-11 43.54 Carbonic anhydrase IV CA4 NM_000717.2 1.46E-06 36.98 Opticin OPTC NM_014359.3 4.78E-08 32.73 Retinol dehydrogenase 5 (11-cis/9-cis) RDH5 NM_002905.2 6.41E-07 26.23 Secreted frizzled-related protein 5 SFRP5 NM_003015.2 2.31E-08 25.48 Retinal outer segment membrane protein 1 ROM1 NM_000327.2 2.33E-06 15.08 Paired box 6, transcript variant 2 PAX6 NM_001604.3 1.03E-06 15.02 Bestrophin 2 BEST2 NM_017682.2 4.10E-09 12.70 Solute carrier family 45, member 2, transcript variant 1 SLC45A2 NM_016180.3 8.30E-09 12.12 Retina and anterior neural fold homeobox RAX NM_013435.2 7.62E-06 10.93 Retinol dehydrogenase 10 (all-trans) RDH10 NM_172037.2 1.34E-05 10.35 Retinal pigment epithelium-derived rhodopsin homolog RRH NM_006583.2 1.07E-06 10.16 Amine oxidase, copper containing 2 (retina-specific) AOC2 NM_001158.3 1.92E-08 9.48 Nervous system development Purkinje cell protein 4 PCP4 NM_006198.2 1.33E-05 70.59 Aldehyde dehydrogenase 1 family, member A2 ALDH1A2 NM_170697.1 5.08E-08 32.32 CD24 molecule CD24 NM_013230.2 1.46E-06 26.74 Endothelin 3 EDN3 NM_207032.1 1.89E-07 20.69 Cholinergic receptor, nicotinic, alpha 3. CHRNA3 NM_000743.2 1.24E-07 20.44 Cadherin 1, type 1, E-cadherin (epithelial) CDH1 NM_004360.2 1.47E-10 19.71 SRY (sex determining region Y)-box 10 SOX10 NM_006941.3 1.40E-08 18.40 Fas apoptotic inhibitory molecule 2 FAIM2 NM_012306.2 1.31E-05 15.84 Paired-like homeodomain 2 PITX2 NM_000325.5 2.63E-08 13.76 Chondroitin sulfate proteoglycan 5 (neuroglycan C) CSPG5 NM_006574.3 1.09E-08 11.41 Reelin RELN NM_173054.1 2.62E-07 10.15 NDRG family member 2 NDRG2 NM_201539.1 1.39E-05 9.86 Microtubule-associated protein tau MAPT NM_016841.2 5.61E-06 9.37 Transcription factor AP-2 alpha (activating enhancer TFAP2A NM_001032280.23.27E-10 9.36 binding protein 2 alpha) Metabolism 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2 HMGCS2 NM_005518.2 1.68E-09 57.48 (mitochondrial) Beta-carotene 15,15'-monooxygenase 1 BCMO1 NM_017429.2 5.50E-08 40.13 Solute carrier family 16, member 8 (monocarboxylic SLC16A8 NM_013356.2 1.49E-08 36.63 acid transporter 3) Apolipoprotein D APOD NM_001647.2 1.30E-05 36.59 Hydroxysteroid (17-beta) dehydrogenase 2 HSD17B2 NM_002153.1 1.86E-08 27.33 Creatine kinase, muscle CKM NM_001824.2 7.76E-10 17.97 ATPase, H+ transporting, lysosomal 42kDa, V1 ATP6V1C2 NM_144583.3 3.47E-09 16.28 ATPase, Na+/K+ transporting, beta 1 polypeptide ATP1B1 NM_001677.3 3.03E-07 13.73 Kallikrein-related peptidase 1 KLK11 NM_144947.1 1.28E-08 12.52 Solute carrier family 23 (nucleobase transporters), SLC23A2 NM_203327.1 9.22E-09 11.62 member 2 Carbonic anhydrase XIV CA14 NM_012113.1 7.77E-09 10.63 ATPase, class V, type 10B ATP10B NM_025153.2 7.15E-09 10.15 Tryptase alpha/beta 1 TPSAB1 NM_003294.3 1.33E-06 9.82 Transport Transthyretin (prealbumin, amyloidosis type I) TTR NM_000371.1 5.79E-11 261.60 Solute carrier family 39 (zinc transporter), member 12 SLC39A12 NM_152725.2 5.31E-11 33.92 Chloride intracellular channel 6 CLIC6 NM_053277.1 6.36E-06 28.99 Transient receptor potential cation channel, subfamily TRPM3 NM_206948.2 4.55E-10 20.14 M, member 3 Downloaded from iovs.arvojournals.org on 10/02/2021 Sodium channel, nonvoltage-gated 1 alpha SCNN1A NM_001038.4 8.88E-08 20.13 Potassium inwardly-rectifying channel, subfamily J, KCNJ13 NM_002242.2 7.96E-08 16.77 member 13 Solute carrier family 29 (nucleoside transporters), SLC29A4 NM_153247.1 2.32E-08 15.68 member 4. Solute carrier family 13 (sodium/sulfate symporters), SLC13A4 NM_012450.2 1.07E-08 13.20 member 4 Snaptoporin SYNPR NM_144642.3 3.31E-07 12.80 Solute carrier family 7, (neutral amino acid transporter, SLC7A10 NM_019849.1 2.23E-08 11.68 y+ system) member 10 Solute carrier family 22 (organic anion transporter), SLC22A8 NM_004254.2 2.61E-07 10.57 member 8 Cell differentiation silver homolog (mouse) SILV NM_006928.3 9.50E-11 195.09 Tyrosinase-related protein 1 TYRP1 NM_000550.1 1.70E-12 127.86 Paired-like homeodomain transcription factor 1 PITX1 NM_002653.3 1.69E-10 59.19 Scavenger receptor class A, member 5 (putative) SCARA5 NM_173833.4 2.23E-09 32.14 Dopachrome tautomerase (dopachrome delta- DCT NM_001922.2 3.47E-10 25.96 isomerase, tyrosine-related protein 2). Collagen, type IX, alpha 1,transcript variant 1 COL9A1 NM_001851.3 9.23E-10 20.14 melanophilin MLPH NM_001042467.15.79E-08 20.10 Glyceraldehyde-3-phosphate dehydrogenase, GAPDHS NM_014364.3 3.12E-09 19.99 spermatogenic Death associated protein-like 1 DAPL1 NM_001017920.15.26E-06 16.89 ATPase, Ca++ transporting, cardiac muscle, fast ATP2A1 NM_173201.2 2.30E-10 16.63 Cbp/p300-interacting transactivator, with Glu/Asp-rich CITED1 NM_004143.2 4.80E-08 15.58 carboxy-terminal domain, 1 EGF-like-domain, multiple 6 EGFL6 NM_015507.2 4.85E-06 14.95 Folate receptor 1 (adult) FOLR1 NM_016724.1 6.05E-08 13.79 Chromosome 4 open reading frame 31 C4orf31 NM_024574.3 9.11E-08 13.17 Septin 3 SEPT3 NM_019106.4 3.15E-07 9.74 Signaling Ectonucleotide pyrophosphatase/phosphodiesterase 2 ENPP2 NM_001040092.11.50E-07 22.17 (autotaxin) Gastrin-releasing peptide GRP NM_001012513.15.67E-06 14.45 DNA-damage-inducible transcript 4-like DDIT4L NM_145244.2 1.36E-07 12.68 Proenkephalin PENK NM_006211.2 4.66E-08 9.39 Anatomical structure development Sclerostin domain containing 1 SOSTDC1 NM_015464.2 1.90E-10 21.94 Myocilin, trabecular meshwork inducible glucocorticoid MYOC NM_000261.1 6.98E-11 19.44 response Forkhead box Q1 FOXQ1 NM_033260.3 1.16E-05 9.53 Development LIM domain only 1 (rhombotin 1) LMO1 NM_002315.1 2.75E-09 15.24 Immune response C3 and PZP-like, alpha-2-macroglobulin domain CPAMD8 NM_015692.2 7.50E-09 11.03 Stress response Tissue factor pathway inhibitor 2 TFPI2 NM_006528.2 5.34E-10 14.24 Unknown Hypothetical protein LOC285016 LOC285016 NM_001002919.15.63E-12 61.44 Melan-A MLANA NM_005511.1 5.76E-10 54.58 Tetraspanin 10 TSPAN10 NM_031945.3 1.06E-08 50.66 Similar to F-box only protein 2 LOC342897 NM_001001414.11.04E-10 27.96 Chromosome 2 open reading frame 40 C2orf40 NM_032411.1 9.17E-07 19.66 Mo sapiens FLJ42875 protein FLJ42875 XM_932794.1 1.25E-09 16.51 Transmembrane protein with EGF-like and two TMEFF2 NM_016192.2 8.16E-10 15.30 follistatin-like domains 2 CDNA FLJ38396 fis, clone FEBRA2007957 EST AK095715 1.07E-05 14.81 Reprimo-like RPRML NM_203400.1 7.86E-10 11.18 Downloaded from iovs.arvojournals.org on 10/02/2021 Supplementary Table 2. Top Key Biological Functions Related to Genes Upregulated in Expression in FVMs Compared to Retina Focus Functions Molecules in Network Score Molecules ADAMTS9,ANXA2,C1q,CD93,COL1A2,COL1A1 (includes EG:1277),COL4A1,collagen, Connective Tissue Disorders, Cellular Collagen Alpha1,Cyclin D,Ecm,ECM1(includesEG:100332249), ERK1/2,FAP,Fibrin, Assembly and Organization, Cellular HSD11B2,IGFBP3,Igfbp,IL-1R,ITGA11,LOX,LRRC32,MMP11,Nuclear 41 22 Function and Maintenance factor1,POSTN,SH2B3,Smad2/3, Smad2/3Smad4,SPRY4,SULF1,TFPI,Tgf beta,TNC (includes EG:116640),TRAM2,VCAN Alpha catenin,CCNB2,COL3A1,COL4A2,COL5A1,COL5A2,COL6A3,Collagen type I, Cell Morphology, Cellular Assembly and Collagen type III,Collagen type IV,Collagen Type V,Collagen Type VI,Collagen(s),GPIIB- Organization, Hair and Skin Development IIIA,Integrin,Integrin alpha 3 beta 1,Integrin alpha 4 beta 1,Integrin alpha 5 beta 35 18 and Function 1,Integrin,ITGA1,LAMA4,LAMB1,LAMC1,Laminin1,Laminin2,Laminin,LUM,MMP23B,NFkB (complex),PLAU,SERPINH1,THBS1,THBS2, THY1,TNFAIP6 Humoral Immune Response, Cellular 14-3-3,Actin,Akt,Alp,APLN,Cadherin,CALD1,CDH5,CDH13,DLX5,ESM1,Ifn gamma,Ige, Growth and Proliferation, Hematological IL32,JAG1,Mlc,MYO1B,Nfat (family),NFE2L3,NOX4,Pak,PECAM1,PI3K (family),PIK3CG, 32 19 System Development and Function Rap1,Rock,TCR,TES,Tnf,TNFRSF4,TNFSF4,TOP2A,TPM4,Tropomyosin,TRPC6 Ca2+,CACNA2D2,CALU,CAST,EBF2,EEF1B2,FKBP2,FKBP8,FKBP1A,GIPR,GLP1R,HAS Cell-To-Cell Signaling and Interaction, 2,HAUS4,KDELR3,KISS1,NEFM,PAX3,PCSK6,PIN4 (includes EG:43044),POLA1, PPIC, Reproductive System Development and 28 15 PRND,PTMA,PXDN,RAI14,RPP40,SAMD9,TBX15,THBS2,TNC (includes EG:116640), Function, Cell Signaling TPPP3,UBC,USP6,WDR41,YY1 AHR,AVIL,C1QTNF6,C21orf7,CCL23,Ck2,COL14A1,CST1,DNTTIP1,ESR1,ETS1,FOXC1, Cell Morphology, Digestive System GEMIN2,Histone h3,HNF1A,IFNG (includes EG:15978),IL13,Insulin,Interferon alpha, Development and Function, Hepatic System 24 14 LRRC17,NR5A2,OLFML2A,OSM,PAMR1,PCDH17,POU4F1,Proinsulin,PWP2,RNA Development and Function polymerase II,SPATA18,ST8SIA4,SUMO2,TIMP4,TNFAIP8L1,TP53 (includes EG:22059) 26s Proteasome,Alpha tubulin,AMPK,CD36,CDKN1A,Cyclin A,Cytochrome c,DYSF,E2f, Cell Cycle, Cellular Development, Cellular estrogen receptor,Hdac,Histone h4,Ifn,IgG1,IgG,Igm,IL12 (complex),IL12 (family), 23 13 Growth and Proliferation Immunoglobulin,KRT7,N-cor,NLRP3,PHLDA2,PI3K (complex),PRSS23,RUNX1,Rxr, SETD8,SKA2,SP100,SRC (family),Tlr,TRPS1,TSH,UBE2C ANGPT2,Ap1,Calcineurin protein(s),Caspase 3/7,Cg,Collagen type IX,Creb,ERK, Organismal Injury and Abnormalities, Fibrinogen,FJX1,FSH,Growth hormone,HDL,IL1,INHBB,ITGB1,LDL,Lh,MAP2K1/2 16 10 Cardiac Fibrosis, Cardiovascular Disease ,Mek,MMP9,NADPH oxidase,Pdgf (complex),PDGF BB,Pkc(s),PTPRE,SERPINE1, Smad,Sos,SPARC,SPRED1,STAT5a/b,thyroid hormone receptor,Tnf receptor,TRIP11 ADCY,ADORA3,ANO1,Calmodulin,calpain,caspase,CD3,ENTPD1,F2R,FAM48A,FNDC1,F Organismal Injury and Abnormalities, ocal adhesion kinase,G protein alphai,G protein beta gamma,Gpcr,GPR116,Hsp90, 14 9 Respiratory Disease, Molecular Transport Jnk,Mapk,Mmp,P110,P38 MAPK,p85 (pik3r),Pka,PLC,PLC gamma,PPEF1,Pro- inflammatory Cytokine,Rac,Ras,Ras homolog,Sfk,Shc,TRAF6,Vegf Downloaded from iovs.arvojournals.org on 10/02/2021 Supplementary Table 3.
Load more

Recommended publications
  • Genetic Associations Between Voltage-Gated Calcium Channels (Vgccs) and Autism Spectrum Disorder (ASD)
    Liao and Li Molecular Brain (2020) 13:96 https://doi.org/10.1186/s13041-020-00634-0 REVIEW Open Access Genetic associations between voltage- gated calcium channels and autism spectrum disorder: a systematic review Xiaoli Liao1,2 and Yamin Li2* Abstract Objectives: The present review systematically summarized existing publications regarding the genetic associations between voltage-gated calcium channels (VGCCs) and autism spectrum disorder (ASD). Methods: A comprehensive literature search was conducted to gather pertinent studies in three online databases. Two authors independently screened the included records based on the selection criteria. Discrepancies in each step were settled through discussions. Results: From 1163 resulting searched articles, 28 were identified for inclusion. The most prominent among the VGCCs variants found in ASD were those falling within loci encoding the α subunits, CACNA1A, CACNA1B, CACN A1C, CACNA1D, CACNA1E, CACNA1F, CACNA1G, CACNA1H, and CACNA1I as well as those of their accessory subunits CACNB2, CACNA2D3, and CACNA2D4. Two signaling pathways, the IP3-Ca2+ pathway and the MAPK pathway, were identified as scaffolds that united genetic lesions into a consensus etiology of ASD. Conclusions: Evidence generated from this review supports the role of VGCC genetic variants in the pathogenesis of ASD, making it a promising therapeutic target. Future research should focus on the specific mechanism that connects VGCC genetic variants to the complex ASD phenotype. Keywords: Autism spectrum disorder, Voltage-gated calcium
    [Show full text]
  • Epha4/Tie2 Crosstalk Regulates Leptomeningeal Collateral Remodeling Following Ischemic Stroke
    EphA4/Tie2 crosstalk regulates leptomeningeal collateral remodeling following ischemic stroke Benjamin Okyere, … , John B. Matson, Michelle H. Theus J Clin Invest. 2019. https://doi.org/10.1172/JCI131493. Research In-Press Preview Neuroscience Vascular biology Leptomeningeal anastomoses or pial collateral vessels play a critical role in cerebral blood flow (CBF) restoration following ischemic stroke. The magnitude of this adaptive response is postulated to be controlled by the endothelium, although the underlying molecular mechanisms remain under investigation. Here we demonstrated that endothelial genetic deletion, using EphA4f/f/Tie2-Cre and EphA4f/f/VeCahderin-CreERT2 mice and vessel painting strategies, implicated EphA4 receptor tyrosine kinase as a major suppressor of pial collateral remodeling, CBF and functional recovery following permanent middle cerebral artery occlusion. Pial collateral remodeling is limited by the cross talk between EphA4-Tie2 signaling in vascular endothelial cells, which is mediated through p-Akt regulation. Furthermore, peptide inhibition of EphA4 resulted in acceleration of the pial arteriogenic response. Our findings demonstrate EphA4 is a negative regulator of Tie2 receptor signaling which limits pial collateral arteriogenesis following cerebrovascular occlusion. Therapeutic targeting of EphA4 and/or Tie2 represents an attractive new strategy for improving collateral function, neural tissue health and functional recovery following ischemic stroke. Find the latest version: https://jci.me/131493/pdf 1 EphA4/Tie2
    [Show full text]
  • FKBP2 Antibody Cat
    FKBP2 Antibody Cat. No.: 23-414 FKBP2 Antibody Western blot analysis of extracts of various cell lines, using FKBP2 antibody (23-414) at 1:1000 dilution. Secondary antibody: HRP Goat Anti-Rabbit IgG (H+L) at 1:10000 dilution. Lysates/proteins: 25ug per lane. Blocking buffer: 3% nonfat dry milk in TBST. Detection: ECL Basic Kit. Exposure time: 90s. Specifications HOST SPECIES: Rabbit SPECIES REACTIVITY: Human, Mouse, Rat Recombinant fusion protein containing a sequence corresponding to amino acids 22-142 IMMUNOGEN: of human FKBP2 (NP_004461.2). TESTED APPLICATIONS: IF, IHC, WB October 2, 2021 1 https://www.prosci-inc.com/fkbp2-antibody-23-414.html WB: ,1:500 - 1:2000 APPLICATIONS: IHC: ,1:100 - 1:200 IF: ,1:50 - 1:200 POSITIVE CONTROL: 1) MCF7 2) SKOV3 3) Jurkat 4) HeLa 5) Mouse thymus 6) Mouse liver PREDICTED MOLECULAR Observed: 14kDa WEIGHT: Properties PURIFICATION: Affinity purification CLONALITY: Polyclonal ISOTYPE: IgG CONJUGATE: Unconjugated PHYSICAL STATE: Liquid BUFFER: PBS with 0.02% sodium azide, 50% glycerol, pH7.3. STORAGE CONDITIONS: Store at -20˚C. Avoid freeze / thaw cycles. Additional Info OFFICIAL SYMBOL: FKBP2 FKBP-13, FKBP13, PPIase, peptidyl-prolyl cis-trans isomerase FKBP2, 13 kDa FK506-binding protein, 13 kDa FKBP, FK506 binding protein 2, 13kDa, FK506-binding protein 2, PPIase ALTERNATE NAMES: FKBP2, epididymis secretory sperm binding protein, immunophilin FKBP13, proline isomerase, rapamycin-binding protein, rotamase GENE ID: 2286 USER NOTE: Optimal dilutions for each application to be determined by the researcher. Background and References October 2, 2021 2 https://www.prosci-inc.com/fkbp2-antibody-23-414.html The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking.
    [Show full text]
  • The Mineralocorticoid Receptor Leads to Increased Expression of EGFR
    www.nature.com/scientificreports OPEN The mineralocorticoid receptor leads to increased expression of EGFR and T‑type calcium channels that support HL‑1 cell hypertrophy Katharina Stroedecke1,2, Sandra Meinel1,2, Fritz Markwardt1, Udo Kloeckner1, Nicole Straetz1, Katja Quarch1, Barbara Schreier1, Michael Kopf1, Michael Gekle1 & Claudia Grossmann1* The EGF receptor (EGFR) has been extensively studied in tumor biology and recently a role in cardiovascular pathophysiology was suggested. The mineralocorticoid receptor (MR) is an important efector of the renin–angiotensin–aldosterone‑system and elicits pathophysiological efects in the cardiovascular system; however, the underlying molecular mechanisms are unclear. Our aim was to investigate the importance of EGFR for MR‑mediated cardiovascular pathophysiology because MR is known to induce EGFR expression. We identifed a SNP within the EGFR promoter that modulates MR‑induced EGFR expression. In RNA‑sequencing and qPCR experiments in heart tissue of EGFR KO and WT mice, changes in EGFR abundance led to diferential expression of cardiac ion channels, especially of the T‑type calcium channel CACNA1H. Accordingly, CACNA1H expression was increased in WT mice after in vivo MR activation by aldosterone but not in respective EGFR KO mice. Aldosterone‑ and EGF‑responsiveness of CACNA1H expression was confrmed in HL‑1 cells by Western blot and by measuring peak current density of T‑type calcium channels. Aldosterone‑induced CACNA1H protein expression could be abrogated by the EGFR inhibitor AG1478. Furthermore, inhibition of T‑type calcium channels with mibefradil or ML218 reduced diameter, volume and BNP levels in HL‑1 cells. In conclusion the MR regulates EGFR and CACNA1H expression, which has an efect on HL‑1 cell diameter, and the extent of this regulation seems to depend on the SNP‑216 (G/T) genotype.
    [Show full text]
  • Aquaporin Channels in the Heart—Physiology and Pathophysiology
    International Journal of Molecular Sciences Review Aquaporin Channels in the Heart—Physiology and Pathophysiology Arie O. Verkerk 1,2,* , Elisabeth M. Lodder 2 and Ronald Wilders 1 1 Department of Medical Biology, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; [email protected] 2 Department of Experimental Cardiology, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; [email protected] * Correspondence: [email protected]; Tel.: +31-20-5664670 Received: 29 March 2019; Accepted: 23 April 2019; Published: 25 April 2019 Abstract: Mammalian aquaporins (AQPs) are transmembrane channels expressed in a large variety of cells and tissues throughout the body. They are known as water channels, but they also facilitate the transport of small solutes, gasses, and monovalent cations. To date, 13 different AQPs, encoded by the genes AQP0–AQP12, have been identified in mammals, which regulate various important biological functions in kidney, brain, lung, digestive system, eye, and skin. Consequently, dysfunction of AQPs is involved in a wide variety of disorders. AQPs are also present in the heart, even with a specific distribution pattern in cardiomyocytes, but whether their presence is essential for proper (electro)physiological cardiac function has not intensively been studied. This review summarizes recent findings and highlights the involvement of AQPs in normal and pathological cardiac function. We conclude that AQPs are at least implicated in proper cardiac water homeostasis and energy balance as well as heart failure and arsenic cardiotoxicity. However, this review also demonstrates that many effects of cardiac AQPs, especially on excitation-contraction coupling processes, are virtually unexplored.
    [Show full text]
  • 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.
    [Show full text]
  • Investigation of Copy Number Variations on Chromosome 21 Detected by Comparative Genomic Hybridization
    Li et al. Molecular Cytogenetics (2018) 11:42 https://doi.org/10.1186/s13039-018-0391-3 RESEARCH Open Access Investigation of copy number variations on chromosome 21 detected by comparative genomic hybridization (CGH) microarray in patients with congenital anomalies Wenfu Li, Xianfu Wang and Shibo Li* Abstract Background: The clinical features of Down syndrome vary among individuals, with those most common being congenital heart disease, intellectual disability, developmental abnormity and dysmorphic features. Complex combination of Down syndrome phenotype could be produced by partially copy number variations (CNVs) on chromosome 21 as well. By comparing individual with partial CNVs of chromosome 21 with other patients of known CNVs and clinical phenotypes, we hope to provide a better understanding of the genotype-phenotype correlation of chromosome 21. Methods: A total of 2768 pediatric patients sample collected at the Genetics Laboratory at Oklahoma University Health Science Center were screened using CGH Microarray for CNVs on chromosome 21. Results: We report comprehensive clinical and molecular descriptions of six patients with microduplication and seven patients with microdeletion on the long arm of chromosome 21. Patients with microduplication have varied clinical features including developmental delay, microcephaly, facial dysmorphic features, pulmonary stenosis, autism, preauricular skin tag, eye pterygium, speech delay and pain insensitivity. We found that patients with microdeletion presented with developmental delay, microcephaly, intrauterine fetal demise, epilepsia partialis continua, congenital coronary anomaly and seizures. Conclusion: Three patients from our study combine with four patients in public database suggests an association between 21q21.1 microduplication of CXADR gene and patients with developmental delay. One patient with 21q22.13 microdeletion of DYRK1A shows association with microcephaly and scoliosis.
    [Show full text]
  • 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.
    [Show full text]
  • Prox1regulates the Subtype-Specific Development of Caudal Ganglionic
    The Journal of Neuroscience, September 16, 2015 • 35(37):12869–12889 • 12869 Development/Plasticity/Repair Prox1 Regulates the Subtype-Specific Development of Caudal Ganglionic Eminence-Derived GABAergic Cortical Interneurons X Goichi Miyoshi,1 Allison Young,1 Timothy Petros,1 Theofanis Karayannis,1 Melissa McKenzie Chang,1 Alfonso Lavado,2 Tomohiko Iwano,3 Miho Nakajima,4 Hiroki Taniguchi,5 Z. Josh Huang,5 XNathaniel Heintz,4 Guillermo Oliver,2 Fumio Matsuzaki,3 Robert P. Machold,1 and Gord Fishell1 1Department of Neuroscience and Physiology, NYU Neuroscience Institute, Smilow Research Center, New York University School of Medicine, New York, New York 10016, 2Department of Genetics & Tumor Cell Biology, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105, 3Laboratory for Cell Asymmetry, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan, 4Laboratory of Molecular Biology, Howard Hughes Medical Institute, GENSAT Project, The Rockefeller University, New York, New York 10065, and 5Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 Neurogliaform (RELNϩ) and bipolar (VIPϩ) GABAergic interneurons of the mammalian cerebral cortex provide critical inhibition locally within the superficial layers. While these subtypes are known to originate from the embryonic caudal ganglionic eminence (CGE), the specific genetic programs that direct their positioning, maturation, and integration into the cortical network have not been eluci- dated. Here, we report that in mice expression of the transcription factor Prox1 is selectively maintained in postmitotic CGE-derived cortical interneuron precursors and that loss of Prox1 impairs the integration of these cells into superficial layers. Moreover, Prox1 differentially regulates the postnatal maturation of each specific subtype originating from the CGE (RELN, Calb2/VIP, and VIP).
    [Show full text]
  • Single-Cell RNA Sequencing Demonstrates the Molecular and Cellular Reprogramming of Metastatic Lung Adenocarcinoma
    ARTICLE https://doi.org/10.1038/s41467-020-16164-1 OPEN Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma Nayoung Kim 1,2,3,13, Hong Kwan Kim4,13, Kyungjong Lee 5,13, Yourae Hong 1,6, Jong Ho Cho4, Jung Won Choi7, Jung-Il Lee7, Yeon-Lim Suh8,BoMiKu9, Hye Hyeon Eum 1,2,3, Soyean Choi 1, Yoon-La Choi6,10,11, Je-Gun Joung1, Woong-Yang Park 1,2,6, Hyun Ae Jung12, Jong-Mu Sun12, Se-Hoon Lee12, ✉ ✉ Jin Seok Ahn12, Keunchil Park12, Myung-Ju Ahn 12 & Hae-Ock Lee 1,2,3,6 1234567890():,; Advanced metastatic cancer poses utmost clinical challenges and may present molecular and cellular features distinct from an early-stage cancer. Herein, we present single-cell tran- scriptome profiling of metastatic lung adenocarcinoma, the most prevalent histological lung cancer type diagnosed at stage IV in over 40% of all cases. From 208,506 cells populating the normal tissues or early to metastatic stage cancer in 44 patients, we identify a cancer cell subtype deviating from the normal differentiation trajectory and dominating the metastatic stage. In all stages, the stromal and immune cell dynamics reveal ontological and functional changes that create a pro-tumoral and immunosuppressive microenvironment. Normal resident myeloid cell populations are gradually replaced with monocyte-derived macrophages and dendritic cells, along with T-cell exhaustion. This extensive single-cell analysis enhances our understanding of molecular and cellular dynamics in metastatic lung cancer and reveals potential diagnostic and therapeutic targets in cancer-microenvironment interactions. 1 Samsung Genome Institute, Samsung Medical Center, Seoul 06351, Korea.
    [Show full text]
  • Retinal Pigment Epithelium Protein of 65 Kda Gene
    Molecular Vision 2013; 19:2312-2320 <http://www.molvis.org/molvis/v19/2312> © 2013 Molecular Vision Received 31 July 2013 | Accepted 14 November 2013 | Published 16 November 2013 Retinal pigment epithelium protein of 65 kDA gene-linked retinal degeneration is not modulated by chicken acidic leucine-rich epidermal growth factor-like domain containing brain protein/ Neuroglycan C/ chondroitin sulfate proteoglycan 5 Sandra Cottet,1,2 René Jüttner,3 Nathalie Voirol,1 Pierre Chambon,4 Fritz G. Rathjen,3 Daniel F. Schorderet,1,2,5 Pascal Escher1,2 1Institute for Research in Ophthalmology, Sion, Switzerland; 2Department of Ophthalmology, University of Lausanne, Lausanne, Switzerland; 3Max-Delbrück-Centrum, Berlin, Germany; 4Institut de Génétique et de Biologie Moléculaire et Cellulaire, Collège de France, Strasbourg, France; 5EPFL-Ecole Polytechnique Fédérale, Lausanne, Switzerland Purpose: To analyze in vivo the function of chicken acidic leucine-rich epidermal growth factor-like domain containing brain protein/Neuroglycan C (gene symbol: Cspg5) during retinal degeneration in the Rpe65−/− mouse model of Leber congenital amaurosis. Methods: We resorted to mice with targeted deletions in the Cspg5 and retinal pigment epithelium protein of 65 kDa (Rpe65) genes (Cspg5−/−/Rpe65−/−). Cone degeneration was assessed with cone-specific peanut agglutinin staining. Tran- scriptional expression of rhodopsin (Rho), S-opsin (Opn1sw), M-opsin (Opn1mw), rod transducin α subunit (Gnat1), and cone transducin α subunit (Gnat2) genes was assessed with quantitative PCR from 2 weeks to 12 months. The retinal pigment epithelium (RPE) was analyzed at P14 with immunodetection of the retinol-binding protein membrane receptor Stra6. Results: No differences in the progression of retinal degeneration were observed between the Rpe65−/− and Cspg5−/−/ Rpe65−/− mice.
    [Show full text]
  • Supplementary Table S5. Differentially Expressed Gene Lists of PD-1High CD39+ CD8 Tils According to 4-1BB Expression Compared to PD-1+ CD39- CD8 Tils
    BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) J Immunother Cancer Supplementary Table S5. Differentially expressed gene lists of PD-1high CD39+ CD8 TILs according to 4-1BB expression compared to PD-1+ CD39- CD8 TILs Up- or down- regulated genes in Up- or down- regulated genes Up- or down- regulated genes only PD-1high CD39+ CD8 TILs only in 4-1BBneg PD-1high CD39+ in 4-1BBpos PD-1high CD39+ CD8 compared to PD-1+ CD39- CD8 CD8 TILs compared to PD-1+ TILs compared to PD-1+ CD39- TILs CD39- CD8 TILs CD8 TILs IL7R KLRG1 TNFSF4 ENTPD1 DHRS3 LEF1 ITGA5 MKI67 PZP KLF3 RYR2 SIK1B ANK3 LYST PPP1R3B ETV1 ADAM28 H2AC13 CCR7 GFOD1 RASGRP2 ITGAX MAST4 RAD51AP1 MYO1E CLCF1 NEBL S1PR5 VCL MPP7 MS4A6A PHLDB1 GFPT2 TNF RPL3 SPRY4 VCAM1 B4GALT5 TIPARP TNS3 PDCD1 POLQ AKAP5 IL6ST LY9 PLXND1 PLEKHA1 NEU1 DGKH SPRY2 PLEKHG3 IKZF4 MTX3 PARK7 ATP8B4 SYT11 PTGER4 SORL1 RAB11FIP5 BRCA1 MAP4K3 NCR1 CCR4 S1PR1 PDE8A IFIT2 EPHA4 ARHGEF12 PAICS PELI2 LAT2 GPRASP1 TTN RPLP0 IL4I1 AUTS2 RPS3 CDCA3 NHS LONRF2 CDC42EP3 SLCO3A1 RRM2 ADAMTSL4 INPP5F ARHGAP31 ESCO2 ADRB2 CSF1 WDHD1 GOLIM4 CDK5RAP1 CD69 GLUL HJURP SHC4 GNLY TTC9 HELLS DPP4 IL23A PITPNC1 TOX ARHGEF9 EXO1 SLC4A4 CKAP4 CARMIL3 NHSL2 DZIP3 GINS1 FUT8 UBASH3B CDCA5 PDE7B SOGA1 CDC45 NR3C2 TRIB1 KIF14 TRAF5 LIMS1 PPP1R2C TNFRSF9 KLRC2 POLA1 CD80 ATP10D CDCA8 SETD7 IER2 PATL2 CCDC141 CD84 HSPA6 CYB561 MPHOSPH9 CLSPN KLRC1 PTMS SCML4 ZBTB10 CCL3 CA5B PIP5K1B WNT9A CCNH GEM IL18RAP GGH SARDH B3GNT7 C13orf46 SBF2 IKZF3 ZMAT1 TCF7 NECTIN1 H3C7 FOS PAG1 HECA SLC4A10 SLC35G2 PER1 P2RY1 NFKBIA WDR76 PLAUR KDM1A H1-5 TSHZ2 FAM102B HMMR GPR132 CCRL2 PARP8 A2M ST8SIA1 NUF2 IL5RA RBPMS UBE2T USP53 EEF1A1 PLAC8 LGR6 TMEM123 NEK2 SNAP47 PTGIS SH2B3 P2RY8 S100PBP PLEKHA7 CLNK CRIM1 MGAT5 YBX3 TP53INP1 DTL CFH FEZ1 MYB FRMD4B TSPAN5 STIL ITGA2 GOLGA6L10 MYBL2 AHI1 CAND2 GZMB RBPJ PELI1 HSPA1B KCNK5 GOLGA6L9 TICRR TPRG1 UBE2C AURKA Leem G, et al.
    [Show full text]