The Human Pancreatic Islet Transcriptome: Expression of Candidate Genes for Type 1 Diabetes and the Impact of Pro-Inflammatory Cytokines

1. ToddJA 2010 Etiology of type 1 diabetes. Immunity 32 457 467

2. EizirikDLColliMLOrtisF 2009 The role of inflammation in insulitis and β-cell loss in type 1 diabetes. Nat Rev Endocrinol 5 219 226

3. NorrisJM 2010 Infant and childhood diet and type 1 diabetes risk: recent advances and prospects. Curr Diab Rep 10 345 349

4. BoettlerTvon HerrathM 2011 Protection against or triggering of Type 1 diabetes? Different roles for viral infections. Expert Rev Clin Immunol 7 45 53

5. MooreFColliMLCnopMEsteveMICardozoAK 2009 PTPN2, a candidate gene for type 1 diabetes, modulates interferon-γ-induced pancreatic β-cell apoptosis. Diabetes 58 1283 1291

6. ColliMLMooreFGurzovENOrtisFEizirikDL 2010 MDA5 and PTPN2, two candidate genes for type 1 diabetes, modify pancreatic β-cell responses to the viral by-product double-stranded RNA. Hum Mol Genet 19 135 146

7. ColliMLNogueiraTCAllagnatFCunhaDAGurzovEN 2011 Exposure to the viral by-product dsRNA or Coxsackievirus B5 triggers pancreatic β cell apoptosis via a Bim/Mcl-1 imbalance. PLoS Pathog 7 e1002267 doi:10.1371/journal.ppat.1002267

8. EizirikDLMooreFFlamezDOrtisF 2008 Use of a systems biology approach to understand pancreatic β-cell death in Type 1 diabetes. Biochem Soc Trans 36 321 327

9. OrtisFNaamaneNFlamezDLadriereLMooreF 2010 Cytokines interleukin-1β and tumor necrosis factor-α regulate different transcriptional and alternative splicing networks in primary β-cells. Diabetes 59 358 374

10. GurzovENBarthsonJMarhfourIOrtisFNaamaneN 2011 Pancreatic β-cells activate a JunB/ATF3-dependent survival pathway during inflammation. Oncogene Epub ahead of print

11. RichardHSchulzMHSultanMNurnbergerASchrinnerS 2010 Prediction of alternative isoforms from exon expression levels in RNA-Seq experiments. Nucleic Acids Res 38 e112

12. SultanMSchulzMHRichardHMagenAKlingenhoffA 2008 A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome. Science 321 956 960

13. TangFBarbacioruCNordmanELiBXuN 2010 RNA-Seq analysis to capture the transcriptome landscape of a single cell. Nat Protoc 5 516 535

14. van BakelHNislowCBlencoweBJHughesTR 2010 Most “dark matter” transcripts are associated with known genes. PLoS Biol 8 e1000371 doi:10.1371/journal.pbio.1000371

15. PanQShaiOLeeLJFreyBJBlencoweBJ 2008 Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat Genet 40 1413 1415

16. WangZGersteinMSnyderM 2009 RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet 10 57 63

17. ModrekBLeeC 2002 A genomic view of alternative splicing. Nat Genet 30 13 19

18. SugnetCWSrinivasanKClarkTAO'BrienGClineMS 2006 Unusual intron conservation near tissue-regulated exons found by splicing microarrays. PLoS Comput Biol 2 e4 doi:10.1371/journal.pcbi.0020004

19. LeKMitsourasKRoyMWangQXuQ 2004 Detecting tissue-specific regulation of alternative splicing as a qualitative change in microarray data. Nucleic Acids Res 32 e180

20. CooperTAWanLDreyfussG 2009 RNA and disease. Cell 136 777 793

21. ConcannonPRichSSNepomGT 2009 Genetics of type 1A diabetes. N Engl J Med 360 1646 1654

22. GurzovENOrtisFCunhaDAGossetGLiM 2009 Signaling by IL-1β+IFN-γ and ER stress converge on DP5/Hrk activation: a novel mechanism for pancreatic β-cell apoptosis. Cell Death Differ 16 1539 1550

23. GurzovENGermanoCMCunhaDAOrtisFVanderwindenJM 2010 p53 up-regulated modulator of apoptosis (PUMA) activation contributes to pancreatic β-cell apoptosis induced by proinflammatory cytokines and endoplasmic reticulum stress. J Biol Chem 285 19910 19920

24. CunhaDALadrièreLOrtisFIgoillo-EsteveMGurzovEN 2009 Glucagon-like peptide-1 agonists protect pancreatic β-cells from lipotoxic endoplasmic reticulum stress through upregulation of BiP and JunB. Diabetes 58 2851 2862

25. MarchettiPBuglianiMLupiRMarselliLMasiniM 2007 The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients. Diabetologia 50 2486 2494

26. CardozoAKOrtisFStorlingJFengYMRasschaertJ 2005 Cytokines downregulate the sarcoendoplasmic reticulum pump Ca2+ ATPase 2b and deplete endoplasmic reticulum Ca2+, leading to induction of endoplasmic reticulum stress in pancreatic β-cells. Diabetes 54 452 461

27. OrtisFCardozoAKCrispimDStorlingJMandrup-PoulsenT 2006 Cytokine-induced proapoptotic gene expression in insulin-producing cells is related to rapid, sustained, and nonoscillatory nuclear factor-κB activation. Mol Endocrinol 20 1867 1879

28. EizirikDLMandrup-PoulsenT 2001 A choice of death - the signal-transduction of immune-mediated beta cell apoptosis. Diabetologia 44 2115 2133

29. BrissovaMFowlerMJNicholsonWEChuAHirshbergB 2005 Assessment of human pancreatic islet architecture and composition by laser scanning confocal microscopy. J Histochem Cytochem 53 1087 1097

30. CabreraOBermanDMKenyonNSRicordiCBerggrenPO 2006 The unique cytoarchitecture of human pancreatic islets has implications for islet cell function. Proc Natl Acad Sci U S A 103 2334 2339

31. AsfariMJanjicDMedaPLiGHalbanPA 1992 Establishment of 2-mercaptoethanol-dependent differentiated insulin-secreting cell lines. Endocrinology 130 167 178

32. KutluBDarvilleMICardozoAKEizirikDL 2003 Molecular regulation of monocyte chemoattractant protein-1 expression in pancreatic β-cells. Diabetes 52 348 355

33. EizirikDLPipeleersDGLingZWelshNHellerstromC 1994 Major species differences between humans and rodents in the susceptibility to pancreatic β-cell injury. Proc Natl Acad Sci U S A 91 9253 9256

34. EizirikDLSandlerSWelshNCetkovic-CvrljeMNiemanA 1994 Cytokines suppress human islet function irrespective of their effects on nitric oxide generation. J Clin Invest 93 1968 1974

35. RasschaertJLadriereLUrbainMDogusanZKatabuaB 2005 Toll-like receptor 3 and STAT-1 contribute to double-stranded RNA+interferon-γ-induced apoptosis in primary pancreatic β-cells. J Biol Chem 280 33984 33991

36. PruittKDTatusovaTMaglottDR 2007 NCBI reference sequences (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins. Nucleic Acids Res 35 D61 65

37. MontgomerySBSammethMGutierrez-ArcelusMLachRPIngleC 2010 Transcriptome genetics using second generation sequencing in a Caucasian population. Nature 464 773 777

38. MortazaviAWilliamsBAMcCueKSchaefferLWoldB 2008 Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods 5 621 628

39. DennisGJrShermanBTHosackDAYangJGaoW 2003 DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol 4 P3

40. AntonovAVDietmannSRodchenkovIMewesHW 2009 PPI spider: a tool for the interpretation of proteomics data in the context of protein-protein interaction networks. Proteomics 9 2740 2749

41. KharroubiIRasschaertJEizirikDLCnopM 2003 Expression of adiponectin receptors in pancreatic β cells. Biochem Biophys Res Commun 312 1118 1122

42. CardozoAKProostPGysemansCChenMCMathieuC 2003 IL-1β and IFN-γ induce the expression of diverse chemokines and IL-15 in human and rat pancreatic islet cells, and in islets from pre-diabetic NOD mice. Diabetologia 46 255 266

43. ArifSMooreFMarksKBouckenoogheTDayanCM 2011 Peripheral and islet interleukin-17 pathway activation characterizes human autoimmune diabetes and promotes cytokine-mediated beta-cell death. Diabetes 60 2112 2119

44. CardozoAKKruhofferMLeemanROrntoftTEizirikDL 2001 Identification of novel cytokine-induced genes in pancreatic β-cells by high-density oligonucleotide arrays. Diabetes 50 909 920

45. KutluBCardozoAKDarvilleMIKruhofferMMagnussonN 2003 Discovery of gene networks regulating cytokine-induced dysfunction and apoptosis in insulin-producing INS-1 cells. Diabetes 52 2701 2719

46. CunhaDAHekermanPLadrièreLBazarra-CastroAOrtisF 2008 Initiation and execution of lipotoxic ER stress in pancreatic β-cells. J Cell Sci 121 2308 2318

47. CnopMLadrièreLHekermanPOrtisFCardozoAK 2007 Selective inhibition of eukaryotic translation initiation factor 2α dephosphorylation potentiates fatty acid-induced endoplasmic reticulum stress and causes pancreatic β-cell dysfunction and apoptosis. J Biol Chem 282 3989 3997

48. PruittKDTatusovaTKlimkeWMaglottDR 2009 NCBI Reference Sequences: current status, policy and new initiatives. Nucleic Acids Res 37 D32 36

49. FurusawaCKanekoK 2003 Zipf's law in gene expression. Phys Rev Lett 90 088102

50. BengtssonMStahlbergARorsmanPKubistaM 2005 Gene expression profiling in single cells from the pancreatic islets of Langerhans reveals lognormal distribution of mRNA levels. Genome Res 15 1388 1392

51. MarchettiPDel GuerraSMarselliLLupiRMasiniM 2004 Pancreatic islets from type 2 diabetic patients have functional defects and increased apoptosis that are ameliorated by metformin. J Clin Endocrinol Metab 89 5535 5541

52. Del GuerraSLupiRMarselliLMasiniMBuglianiM 2005 Functional and molecular defects of pancreatic islets in human type 2 diabetes. Diabetes 54 727 735

53. NagalakshmiUWangZWaernKShouCRahaD 2008 The transcriptional landscape of the yeast genome defined by RNA sequencing. Science 320 1344 1349

54. BarrettJCClaytonDGConcannonPAkolkarBCooperJD 2009 Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet 41 703 707

55. ToddJAWalkerNMCooperJDSmythDJDownesK 2007 Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat Genet 39 857 864

56. SantinIMooreFColliMLGurzovENMarselliL 2011 PTPN2, a candidate gene for type 1 diabetes, modulates pancreatic β-cell apoptosis via regulation of the BH3-only protein Bim. Diabetes 60 3279 3288

57. LenzenS 2008 Oxidative stress: the vulnerable β-cell. Biochem Soc Trans 36 343 347

58. TiedgeMLortzSDrinkgernJLenzenS 1997 Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells. Diabetes 46 1733 1742

59. WelshNMargulisBBorgLAWiklundHJSaldeenJ 1995 Differences in the expression of heat-shock proteins and antioxidant enzymes between human and rodent pancreatic islets: implications for the pathogenesis of insulin-dependent diabetes mellitus. Mol Med 1 806 820

60. YlipaastoPKutluBRasilainenSRasschaertJSalmelaK 2005 Global profiling of coxsackievirus- and cytokine-induced gene expression in human pancreatic islets. Diabetologia 48 1510 1522

61. MooreFNaamaneNColliMLBouckenoogheTOrtisF 2011 STAT1 is a master regulator of pancreatic β-cell apoptosis and islet inflammation. J Biol Chem 286 929 941

62. GrossoARGomesAQBarbosa-MoraisNLCaldeiraSThorneNP 2008 Tissue-specific splicing factor gene expression signatures. Nucleic Acids Res 36 4823 4832

63. ZhangCFriasMAMeleARuggiuMEomT 2010 Integrative modeling defines the Nova splicing-regulatory network and its combinatorial controls. Science 329 439 443

64. JensenKBDredgeBKStefaniGZhongRBuckanovichRJ 2000 Nova-1 regulates neuron-specific alternative splicing and is essential for neuronal viability. Neuron 25 359 371

65. KutluBBurdickDBaxterDRasschaertJFlamezD 2009 Detailed transcriptome atlas of the pancreatic β cell. BMC Med Genomics 2 3

66. DredgeBKDarnellRB 2003 Nova regulates GABA(A) receptor γ2 alternative splicing via a distal downstream UCAU-rich intronic splicing enhancer. Mol Cell Biol 23 4687 4700

67. JelenNUleJZivinMDarnellRB 2007 Evolution of Nova-dependent splicing regulation in the brain. PLoS Genet 3 e173 doi:10.1371/journal.pgen.0030173

68. BradfieldJPQuHQWangKZhangHSleimanPM 2011 A genome-wide meta-analysis of six type 1 diabetes cohorts identifies multiple associated loci. PLoS Genet 7 e1002293 doi:10.1371/journal.pgen.1002293

69. FlorezJC 2008 Newly identified loci highlight beta cell dysfunction as a key cause of type 2 diabetes: Where are the insulin resistance genes? Diabetologia 51 1100 1110

70. McCarthyMI 2010 Genomics, type 2 diabetes, and obesity. N Engl J Med 363 2339 2350

71. ChenMCProostPGysemansCMathieuCEizirikDL 2001 Monocyte chemoattractant protein-1β is expressed in pancreatic islets from prediabetic NOD mice and in interleukin-1-exposed human and rat islet cells. Diabetologia 44 325 332

72. MartinAPGrisottoMGCanasto-ChibuqueCKunkelSLBrombergJS 2008 Islet expression of M3 uncovers a key role for chemokines in the development and recruitment of diabetogenic cells in NOD mice. Diabetes 57 387 394

73. RoepBOKleijwegtFSvan HalterenAGBonatoVBoggiU 2010 Islet inflammation and CXCL10 in recent-onset type 1 diabetes. Clin Exp Immunol 159 338 343

74. UnoSImagawaASaishoKOkitaKIwahashiH 2010 Expression of chemokines, CXC chemokine ligand 10 (CXCL10) and CXCR3 in the inflamed islets of patients with recent-onset autoimmune type 1 diabetes. Endocr J 57 991 996

75. LiuDCardozoAKDarvilleMIEizirikDL 2002 Double-stranded RNA cooperates with interferon-γ and IL-1β to induce both chemokine expression and nuclear factor-κB-dependent apoptosis in pancreatic β-cells: potential mechanisms for viral-induced insulitis and β-cell death in type 1 diabetes mellitus. Endocrinology 143 1225 1234

76. Igoillo-EsteveMMarselliLCunhaDALadriereLOrtisF 2010 Palmitate induces a pro-inflammatory response in human pancreatic islets that mimics CCL2 expression by beta cells in type 2 diabetes. Diabetologia 53 1395 1405

77. SimmonsMJFanGZongWXDegenhardtKWhiteE 2008 Bfl-1/A1 functions, similar to Mcl-1, as a selective tBid and Bak antagonist. Oncogene 27 1421 1428

78. KarsanAYeeEHarlanJM 1996 Endothelial cell death induced by tumor necrosis factor-α is inhibited by the Bcl-2 family member, A1. J Biol Chem 271 27201 27204

79. SarkarSAKutluBVelmuruganKKizaka-KondohSLeeCE 2009 Cytokine-mediated induction of anti-apoptotic genes that are linked to nuclear factor κB (NF-κB) signalling in human islets and in a mouse beta cell line. Diabetologia 52 1092 1101

80. ChenLWillisSNWeiASmithBJFletcherJI 2005 Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol Cell 17 393 403

81. HermanMDNymanTWelinMLehtioLFlodinS 2008 Completing the family portrait of the anti-apoptotic Bcl-2 proteins: crystal structure of human Bfl-1 in complex with Bim. FEBS Lett 582 3590 3594

82. ChenMManleyJL 2009 Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches. Nat Rev Mol Cell Biol 10 741 754

83. HartmannBValcarcelJ 2009 Decrypting the genome's alternative messages. Curr Opin Cell Biol 21 377 386

84. UleJJensenKBRuggiuMMeleAUleA 2003 CLIP identifies Nova-regulated RNA networks in the brain. Science 302 1212 1215

85. SuckowATComolettiDWaldropMAMosedaleMEgodageS 2008 Expression of neurexin, neuroligin, and their cytoplasmic binding partners in the pancreatic beta-cells and the involvement of neuroligin in insulin secretion. Endocrinology 149 6006 6017

86. AtoufFCzernichowPScharfmannR 1997 Expression of neuronal traits in pancreatic β cells. Implication of neuron-restrictive silencing factor/repressor element silencing transcription factor, a neuron-restrictive silencer. J Biol Chem 272 1929 1934

87. CardozoAKBerthouLKruhofferMOrntoftTNicollsMR 2003 Gene microarray study corroborates proteomic findings in rodent islet cells. J Proteome Res 2 553 555

88. MartensGAJiangLHellemansKHStangeGHeimbergH 2011 Clusters of conserved β cell marker genes for assessment of β cell phenotype. PLoS ONE 6 e24134 doi:10.1371/journal.pone.0024134