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Research Newsletter - December 2008

Spotlight

In an article paper published in Science, Konrad Hochedlinger and colleagues report their creation of induced pluripotent stem cells without viral integration.

Induced pluripotent stem cells generated without viral integration.

Abstract:

Pluripotent stem cells have been generated from mouse and human somatic cells by viral expression of the transcription factors Oct4, Sox2, Klf4, and c-Myc. A major limitation of this technology is the use of potentially harmful genome-integrating viruses. We generated mouse induced pluripotent stem (iPS) cells from fibroblasts and liver cells by using nonintegrating adenoviruses transiently expressing Oct4, Sox2, Klf4, and c-Myc. These adenoviral iPS (adeno-iPS) cells show DNA demethylation characteristic of reprogrammed cells, express endogenous pluripotency genes, form teratomas, and contribute to multiple tissues, including the germ line, in chimeric mice. Our results provide strong evidence that insertional mutagenesis is not required for in vitro reprogramming. Adenoviral reprogramming may provide an improved method for generating and studying patient-specific stem cells and for comparing embryonic stem cells and iPS cells.

Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K. Induced pluripotent stem cells generated without viral integration. Science. 2008 Nov 7;322(5903):945-9. Epub 2008 Sep 25. Read Paper.

Scientific Papers

Review and Commentary

  • Bonner-Weir S, O'Brien TD. Islets in type 2 diabetes: in honor of Dr. Robert C. Turner. Diabetes. 2008 Nov;57(11):2899-904. No abstract available. Read Abstract.
  • Eggan K. Using stem cells and reprogramming to understand disease. Regen Med. 2008 Nov;3(6):799-801. Read Abstract.
  • Huang HT, Zon LI. Regulation of Stem Cells in the Zebra Fish Hematopoietic System. Cold Spring Harb Symp Quant Biol. 2008 Nov 6. Read Abstract.
  • Maherali N, Hochedlinger K. Induced Pluripotency of Mouse and Human Somatic Cells. Cold Spring Harb Symp Quant Biol. 2008 Nov 6. Read Abstract.
  • O'Rahilly S, Weir GC, Matthews DR. An appreciation of Robert Turner. Diabetes. 2008 Nov;57(11):2918-21. No abstract available. Read Abstract.
  • Orkin SH, Wang J, Kim J, Chu J, Rao S, Theunissen TW, Shen X, Levasseur DN. The Transcriptional Network Controlling Pluripotency in ES Cells. Cold Spring Harb Symp Quant Biol. 2008 Nov 6. Read Abstract.
  • Raiser DM, Zacharek SJ, Roach RR, Curtis SJ, Sinkevicius KW, Gludish DW, Kim CF. Stem Cell Biology in the Lung and Lung Cancers: Employing Pulmonary Context and Classic Approaches. Cold Spring Harb Symp Quant Biol. 2008 Nov 26. Read Abstract.
  • Zhao R, Daley GQ. From fibroblasts to iPS cells: induced pluripotency by defined factors. J Cell Biochem. 2008 Nov 1;105(4):949-55. Read Abstract.
  • Zhou Q, Melton DA. Pathways to New {beta} Cells. Cold Spring Harb Symp Quant Biol. 2008 Nov 6. Read Abstract.

Blood

  • Fonseca C, Soiffer R, Ho V, Vanneman M, Jinushi M, Ritz J, Neuberg D, Stone R, Deangelo D, Dranoff G. Protein disulfide isomerases are antibody targets during immune-mediated tumor destruction. Blood. 2008 Nov 13. Read Abstract.
  • Kawamata N, Ogawa S, Yamamoto G, Lehmann S, Levine RL, Pikman Y, Nannya Y, Sanada M, Miller CW, Gilliland DG, Koeffler HP. Genetic profiling of myeloproliferative disorders by single-nucleotide polymorphism oligonucleotide microarray. Exp Hematol. 2008 Nov;36(11):1471-9. Epub 2008 Aug 23. Read Abstract.

Cancer

  • Bernard L, Belisle C, Mollica L, Provost S, Roy DC, Gilliland DG, Levine RL, Busque L. Telomere length is severely and similarly reduced in JAK2V617F-positive and -negative myeloproliferative neoplasms. Leukemia. 2008 Nov 13. Read Abstract.
  • Costa DB, Nguyen KS, Cho BC, Sequist LV, Jackman DM, Riely GJ, Yeap BY, Halmos B, Kim JH, J√ɬ§nne PA, Huberman MS, Pao W, Tenen DG, Kobayashi S. Effects of erlotinib in EGFR mutated non-small cell lung cancers with resistance to gefitinib. Clin Cancer Res. 2008 Nov 1;14(21):7060-7. Read Abstract.
  • Cross NC, Daley GQ, Green AR, Hughes TP, Jamieson C, Manley P, Mughal T, Perrotti D, Radich J, Skoda R, Soverini S, Vainchenker W, Verstovsek S, Villeval JL, Goldman JM. BCR-ABL1-positive CML and BCR-ABL1-negative chronic myeloproliferative disorders: some common and contrasting features. Leukemia. 2008 Nov;22(11):1975-89. No abstract available. Read Abstract.
  • Engelman JA, Chen L, Tan X, Crosby K, Guimaraes AR, Upadhyay R, Maira M, McNamara K, Perera SA, Song Y, Chirieac LR, Kaur R, Lightbown A, Simendinger J, Li T, Padera RF, Garc√ɬ≠a-Echeverr√ɬ≠a C, Weissleder R, Mahmood U, Cantley LC, Wong KK. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat Med. 2008 Dec;14(12):1351-6. Epub 2008 Nov 30. Read Abstract.
  • Hingtgen S, Ren X, Terwilliger E, Classon M, Weissleder R, Shah K. Targeting multiple pathways in gliomas with stem cell and viral delivered S-TRAIL and Temozolomide. Mol Cancer Ther. 2008 Nov;7(11):3575-85. Read Abstract.
  • Hoskins EE, Morris TA, Higginbotham JM, Spardy N, Cha E, Kelly P, Williams DA, Wikenheiser-Brokamp KA, Duensing S, Wells SI. Fanconi anemia deficiency stimulates HPV-associated hyperplastic growth in organotypic epithelial raft culture. Oncogene. 2008 Nov 17. Read Abstract.
  • Krivtsov AV, Feng Z, Lemieux ME, Faber J, Vempati S, Sinha AU, Xia X, Jesneck J, Bracken AP, Silverman LB, Kutok JL, Kung AL, Armstrong SA. H3K79 methylation profiles define murine and human MLL-AF4 leukemias. Cancer Cell. 2008 Nov 4;14(5):355-68. Read Abstract.
  • Nasr R, Guillemin MC, Ferhi O, Soilihi H, Peres L, Berthier C, Rousselot P, Robledo-Sarmiento M, Lallemand-Breitenbach V, Gourmel B, Vitoux D, Pandolfi PP, Rochette-Egly C, Zhu J, de Th√ɬ© H. Eradication of acute promyelocytic leukemia-initiating cells through PML-RARA degradation. Nat Med. 2008 Dec;14(12):1333-42. Epub 2008 Nov 23. Read Abstract.
  • W√ɬºrdinger T, Tannous BA, Saydam O, Skog J, Grau S, Soutschek J, Weissleder R, Breakefield XO, Krichevsky AM. miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells. Cancer Cell. 2008 Nov 4;14(5):382-93. Read Abstract.

Cardiovascular System

  • Ma Q, Zhou B, Pu WT. Reassessment of Isl1 and Nkx2-5 cardiac fate maps using a Gata4-based reporter of Cre activity. Dev Biol. 2008 Nov 1;323(1):98-104. Epub 2008 Aug 22. Read Abstract.

Developmental Biology

  • de Jong-Curtain TA, Parslow AC, Trotter AJ, Hall NE, Verkade H, Tabone T, Christie EL, Crowhurst MO, Layton JE, Shepherd IT, Nixon SJ, Parton RG, Zon LI, Stainier DY, Lieschke GJ, Heath JK. Abnormal Nuclear Pore Formation Triggers Apoptosis in the Intestinal Epithelium of elys-Deficient Zebra Fish. Gastroenterology. 2008 Nov 6. Read Abstract.
  • Flores MV, Hall CJ, Davidson AJ, Singh PP, Mahagaonkar AA, Zon LI, Crosier KE, Crosier PS. Intestinal differentiation in zebrafish requires Cdx1b, a functional equivalent of mammalian Cdx2. Gastroenterology. 2008 Nov;135(5):1665-75. Epub 2008 Jul 31. Read Abstract.
  • Fujino A, Arango NA, Zhan Y, Manganaro TF, Li X, Maclaughlin DT, Donahoe PK. Cell migration and activated PI3K/AKT-directed elongation in the developing rat M√ɬºllerian duct. Dev Biol. 2008 Nov 5. Read Abstract.
  • Kanadia RN, Clark VE, Punzo C, Trimarchi JM, Cepko CL. Temporal requirement of the alternative-splicing factor Sfrs1 for the survival of retinal neurons. Development. 2008 Dec;135(23):3923-33. Epub 2008 Nov 5. Read Abstract.
  • Raffel GD, Chu GC, Jesneck JL, Cullen DE, Bronson RT, Bernard OA, Gilliland DG. Ott1(Rbm15) is essential for placental vascular branching morphogenesis and embryonic development of the heart and spleen. Mol Cell Biol. 2008 Nov 3. Read Abstract.
  • Shen X, Liu Y, Hsu YJ, Fujiwara Y, Kim J, Mao X, Yuan GC, Orkin SH. EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency. Mol Cell. 2008 Nov 21;32(4):491-502. Read Abstract.
  • Stenman JM, Rajagopal J, Carroll TJ, Ishibashi M, McMahon J, McMahon AP. Canonical Wnt signaling regulates organ-specific assembly and differentiation of CNS vasculature. Science. 2008 Nov 21;322(5905):1247-50. Read Abstract.
  • Walker JL, Menko AS, Khalil S, Rebustini I, Hoffman MP, Kreidberg JA, Kukuruzinska MA. Diverse roles of E-cadherin in the morphogenesis of the submandibular gland: insights into the formation of acinar and ductal structures. Dev Dyn. 2008 Nov;237(11):3128-41. Read Abstract.

Genetics and Genomics

  • Alazami AM, Al-Saif A, Al-Semari A, Bohlega S, Zlitni S, Alzahrani F, Bavi P, Kaya N, Colak D, Khalak H, Baltus A, Peterlin B, Danda S, Bhatia KP, Schneider SA, Sakati N, Walsh CA, Al-Mohanna F, Meyer B, Alkuraya FS. Mutations in C2orf37, encoding a nucleolar protein, cause hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal syndrome. Am J Hum Genet. 2008 Dec;83(6):684-91. Epub 2008 Nov 20. Read Abstract.
  • Chiara Manzini M, Gleason D, Chang BS, Sean Hill R, Barry BJ, Partlow JN, Poduri A, Currier S, Galvin-Parton P, Shapiro LR, Schmidt K, Davis JG, Basel-Vanagaite L, Seidahmed MZ, Salih MA, Dobyns WB, Walsh CA. Ethnically diverse causes of Walker-Warburg syndrome (WWS): FCMD mutations are a more common cause of WWS outside of the Middle East. Hum Mutat. 2008 Nov;29(11):E231-41. Read Abstract.
  • Ferland RJ, Batiz LF, Neal J, Lian G, Bundock E, Lu J, Hsiao YC, Diamond R, Mei D, Banham AH, Brown PJ, Vanderburg CR, Joseph J, Hecht JL, Folkerth R, Guerrini R, Walsh CA, Rodriguez EM, Sheen VL. Disruption of neural progenitors along the ventricular and subventricular zones in periventricular heterotopia. Hum Mol Genet. 2008 Nov 7. Read Abstract.
  • Parrini E, Ferrari AR, Dorn T, Walsh CA, Guerrini R. Bilateral frontoparietal polymicrogyria, Lennox-Gastaut syndrome, and GPR56 gene mutations. Epilepsia. 2008 Nov 4. Read Abstract.

Imaging

  • Breckwoldt MO, Chen JW, Stangenberg L, Aikawa E, Rodriguez E, Qiu S, Moskowitz MA, Weissleder R. Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase. Proc Natl Acad Sci USA. 2008 Nov 25;105(47):18584-9. Epub 2008 Nov 14. Read Abstract.
  • Cortez-Retamozo V, Swirski FK, Waterman P, Yuan H, Figueiredo JL, Newton AP, Upadhyay R, Vinegoni C, Kohler R, Blois J, Smith A, Nahrendorf M, Josephson L, Weissleder R, Pittet MJ. Real-time assessment of inflammation and treatment response in a mouse model of allergic airway inflammation. J Clin Invest. 2008 Dec;118(12):4058-66. doi: 10.1172/JCI36335. Epub 2008 Nov 6. Read Abstract.
  • Guimaraes AR, Rakhlin E, Weissleder R, Thayer SP. Magnetic resonance imaging monitors physiological changes with antihedgehog therapy in pancreatic adenocarcinoma xenograft model. Pancreas. 2008 Nov;37(4):440-4. Read Abstract.
  • Niedre MJ, de Kleine RH, Aikawa E, Kirsch DG, Weissleder R, Ntziachristos V. Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo. Proc Natl Acad Sci USA. 2008 Dec 9;105(49):19126-31. Epub 2008 Nov 17. Read Abstract.

Immunology

  • Hill JA, Hall JA, Sun CM, Cai Q, Ghyselinck N, Chambon P, Belkaid Y, Mathis D, Benoist C. Retinoic acid enhances Foxp3 induction indirectly by relieving inhibition from CD4+CD44hi Cells. Immunity. 2008 Nov;29(5):758-70. Read Abstract.
  • Nigrovic PA, Gray DH, Jones T, Hallgren J, Kuo FC, Chaletzky B, Gurish M, Mathis D, Benoist C, Lee DM. Genetic inversion in mast cell-deficient (W(sh)) mice interrupts corin and manifests as hematopoietic and cardiac aberrancy. Am J Pathol. 2008 Dec;173(6):1693-701. Epub 2008 Nov 6. Read Abstract.

Nervous System

  • Vinuela A, Hallett PJ, Reske-Nielsen C, Patterson M, Sotnikova TD, Caron MG, Gainetdinov RR, Isacson O. Implanted reuptake-deficient or wild-type dopaminergic neurons improve ON L-dopa dyskinesias without OFF-dyskinesias in a rat model of Parkinson's disease. Brain. 2008 Nov 6. Read Abstract.

Pain

  • Gerner P, Binshtok AM, Wang CF, Hevelone ND, Bean BP, Woolf CJ, Wang GK. Capsaicin combined with local anesthetics preferentially prolongs sensory/nociceptive block in rat sciatic nerve. Anesthesiology. 2008 Nov;109(5):872-8. Read Abstract.

Renal System

  • Brunskill EW, Aronow BJ, Georgas K, Rumballe B, Valerius MT, Aronow J, Kaimal V, Jegga AG, Grimmond S, McMahon AP, Patterson LT, Little MH, Potter SS. Atlas of gene expression in the developing kidney at microanatomic resolution. Dev Cell. 2008 Nov;15(5):781-91. Read Abstract.
  • Chagnon F, Vaidya VS, Plante GE, Bonventre JV, Bernard A, Guindi C, Lesur O. Modulation of aquaporin-2/vasopressin2 receptor kidney expression and tubular injury after endotoxin (lipopolysaccharide) challenge. Crit Care Med. 2008 Nov;36(11):3054-61. Read Abstract.
  • Trujillo J, Cruz C, Tovar A, Vaidya V, Zambrano E, Bonventre JV, Gamba G, Torres N, Bobadilla NA. Renoprotective mechanisms of soy protein intake in the obese Zucker rat. Am J Physiol Renal Physiol. 2008 Nov;295(5):F1574-82. Epub 2008 Sep 24. Read Abstract.

Technology

  • Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K. Induced pluripotent stem cells generated without viral integration. Science. 2008 Nov 7;322(5903):945-9. Epub 2008 Sep 25. Read Abstract.
  • Varas F, Stadtfeld M, De Andres-Aguayo L, Maherali N, di Tullio A, Pantano L, Notredame C, Hochedlinger K, Graf T. Fibroblast derived induced pluripotent stem cells show no common retroviral vector insertions. Stem Cells. 2008 Nov 13. Read Abstract.