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Research Newsletter - October 2008

Spotlight

In an article paper published in Science, Konrad Hochedlinger and HSCI colleagues at Massachusetts General Hospital and Joslin Diabetes Center report having created mouse iPS cells using adenoviruses rather that genome-integrating retroviruses.

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. Here, we generate mouse induced pluripotent stem cells (iPS) 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 Sep 25. Read Paper.

Scientific Papers

Review and Commentary

  • Gartner A, Boag PR, Blackwell TK. Germline survival and apoptosis. WormBook. 2008 Sep 4:1-20. Review. Read Abstract.
  • Kimball AB, Kupper TS. Future perspectives/quo vadis psoriasis treatment? Immunology, pharmacogenomics, and epidemiology. Clin Dermatol. 2008 Sep-Oct;26(5):554-61. Read Abstract.
  • Levine RL, Gilliland DG. Myeloproliferative disorders. Blood. 2008 Sep 15;112(6):2190-8. Read Abstract.
  • Medici D, Hay ED, Olsen BR. Snail and Slug Promote Epithelial-Mesenchymal Transition through {beta}-catenin-TCF-4-dependent Expression of TGF-{beta}3. Mol Biol Cell. 2008 Sep 17. Read Abstract.
  • Pandolfi PP. P-TEN exciting years: from the cytosol to the nucleus and back to keep cancer at bay. Oncogene. 2008 Sep 18;27(41):5386. Read Abstract.
  • Walkley CR, Sankaran VG, Orkin SH. Rb and hematopoiesis: stem cells to anemia. Cell Div. 2008 Sep 8;3:13. Read Abstract.
  • White RM, Zon LI. Melanocytes in development, regeneration, and cancer. Cell Stem Cell. 2008 Sep 11;3(3):242-52. Review. Read Abstract.
  • Williams DA. Sleeping beauty vector system moves toward human trials in the United States. Mol Ther. 2008 Sep;16(9):1515-6. Read Abstract.
  • Zhou B, Pu WT. More than a cover: epicardium as a novel source of cardiac progenitor cells. Regen Med. 2008 Sep;3(5):633-5. Read Abstract.

Blood

  • Ismailoglu I, Yeamans G, Daley GQ, Perlingeiro RC, Kyba M. Mesodermal patterning activity of SCL. Exp Hematol. 2008 Sep 20. Read Abstract.
  • Mercher T, Cornejo MG, Sears C, Kindler T, Moore SA, Maillard I, Pear WS, Aster JC, Gilliland DG. Notch signaling specifies megakaryocyte development from hematopoietic stem cells. Cell Stem Cell. 2008 Sep 11;3(3):314-26. Read Abstract.

Cancer

  • Carracedo A, Ma L, Teruya-Feldstein J, Rojo F, Salmena L, Alimonti A, Egia A, Sasaki AT, Thomas G, Kozma SC, Papa A, Nardella C, Cantley LC, Baselga J, Pandolfi PP. Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. J Clin Invest. 2008 Sep;118(9):3065-74. Read Abstract.
  • Carracedo A, Pandolfi PP. The PTEN-PI3K pathway: of feedbacks and cross-talks. Oncogene. 2008 Sep 18;27(41):5527-41. Read Abstract.
  • Clark RA, Huang SJ, Murphy GF, Mollet IG, Hijnen D, Muthukuru M, Schanbacher CF, Edwards V, Miller DM, Kim JE, Lambert J, Kupper TS. Human squamous cell carcinomas evade the immune response by down-regulation of vascular E-selectin and recruitment of regulatory T cells. J Exp Med. 2008 Sep 29;205(10):2221-34. Epub 2008 Sep 15. Read Abstract.
  • Li L, Dutra A, Pak E, Labrie Iii JE, Gerstein RM, Pandolfi PP, Recht LD, Ross AH. EGFRvIII expression and PTEN loss synergistically induce chromosomal instability and glial tumors. Neuro Oncol. 2008 Sep 23. Read Abstract.
  • Teitell MA, Pandolfi PP. Molecular Genetics of Acute Lymphoblastic Leukemia. Annu Rev Pathol. 2008 Sep 10. Read Abstract.

Cardiovascular System

  • Danielyan K, Ganguly K, Ding BS, Atochin D, Zaitsev S, Murciano JC, Huang PL, Kasner SE, Cines DB, Muzykantov VR. Cerebrovascular thromboprophylaxis in mice by erythrocyte-coupled tissue-type plasminogen activator. Circulation. 2008 Sep 30;118(14):1442-9. Epub 2008 Sep 15. Read Abstract.
  • Pfister O, Oikonomopoulos A, Sereti KI, Sohn RL, Cullen D, Fine GC, Mouquet F, Westerman K, Liao R. Role of the ATP-binding cassette transporter Abcg2 in the phenotype and function of cardiac side population cells. Circ Res. 2008 Oct 10;103(8):825-35. Epub 2008 Sep 11. Read Abstract.

Developmental Biology

  • Azam M, Seeliger MA, Gray NS, Kuriyan J, Daley GQ. Activation of tyrosine kinases by mutation of the gatekeeper threonine. Nat Struct Mol Biol. 2008 Oct;15(10):1109-18. Epub 2008 Sep 14. Read Abstract.
  • Mugford JW, Sipil√¢ÀÜ≈°√Ç¬ß P, McMahon JA, McMahon AP. Osr1 expression demarcates a multi-potent population of intermediate mesoderm that undergoes progressive restriction to an Osr1-dependent nephron progenitor compartment within the mammalian kidney. Dev Biol. 2008 Sep 19. Read Abstract.
  • Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K. Induced Pluripotent Stem Cells Generated Without Viral Integration. Science. 2008 Sep 25. Read Abstract.
  • Trede NS, Ota T, Kawasaki H, Paw BH, Katz T, Demarest B, Hutchinson S, Zhou Y, Hersey C, Zapata A, Amemiya CT, Zon LI. Zebrafish mutants with disrupted early T-cell and thymus development identified in early pressure screen. Dev Dyn. 2008 Sep;237(9):2575-84. 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 Sep 24;237(11):3128-3141. Read Abstract.
  • Wang L, Sewell WF, Kim SD, Shin JT, Macrae CA, Zon LI, Seidman JG, Seidman CE. Eya4 regulation of Na+/K+-ATPase is required for sensory system development in zebrafish. Development. 2008 Oct;135(20):3425-34. Epub 2008 Sep 17. Read Abstract.

Diabetes

  • Gavanescu I, Benoist C, Mathis D. B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients. Proc Natl Acad Sci USA. 2008 Sep 2;105(35):13009-14. Epub 2008 Aug 28. Read Abstract.
  • Guerau-de-Arellano M, Mathis D, Benoist C. Transcriptional impact of Aire varies with cell type. Proc Natl Acad Sci USA. 2008 Sep 16;105(37):14011-6. Epub 2008 Sep 9. Read Abstract.
  • Xu J, Han J, Long YS, Lock J, Weir GC, Epstein PN, Liu YQ. Malic enzyme is present in mouse islets and modulates insulin secretion. Diabetologia. 2008 Sep 19. Read Abstract.

Imaging

  • Korosoglou G, Shah S, Vonken EJ, Gilson WD, Sch√§r M, Tang L, Kraitchman DL, Boston RC, Sosnovik DE, Weiss RG, Weissleder R, Stuber M. Off-resonance angiography: a new method to depict vessels--phantom and rabbit studies. Radiology. 2008 Nov;249(2):501-9. Epub 2008 Sep 9. Read Abstract.

Immunology

  • Cheng S, Hsia CY, Feng B, Liou ML, Fang X, Pandolfi PP, Liou HC. BCR-mediated apoptosis associated with negative selection of immature B cells is selectively dependent on Pten. Cell Res. 2008 Sep 9. Read Abstract.

Molecular Biology

  • Maggi LB Jr, Kuchenruether M, Dadey DY, Schwope RM, Grisendi S, Townsend RR, Pandolfi PP, Weber JD. Nucleophosmin Serves as a Rate-Limiting Nuclear Export Chaperone for the Mammalian Ribosome. Mol Cell Biol. 2008 Sep 22. Read Abstract.
  • Shima Y, Shima T, Chiba T, Irimura T, Pandolfi PP, Kitabayashi I. PML activates transcription by protecting HIPK2 and p300 from SCFFbx3-mediated degradation. Mol Cell Biol. 2008 Sep 22. Read Abstract.

Renal System

  • Trujillo J, Cruz C, Tovar AR, Vaidya VS, 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 Sep 24. Read Abstract.
  • Waanders F, Vaidya VS, Goor HV, Leuvenink H, Damman K, Hamming I, Bonventre JV, Vogt L, Navis G. Effect of Renin-Angiotensin-Aldosterone System Inhibition, Dietary Sodium Restriction, and/or Diuretics on Urinary Kidney Injury Molecule 1 Excretion in Nondiabetic Proteinuric Kidney Disease: A Post Hoc Analysis of a Randomized Controlled Trial. Am J Kidney Dis. 2008 Sep 25. Read Abstract.
  • Waikar SS, Bonventre JV. Biomarkers for the diagnosis of acute kidney injury. Nephron Clin Pract. 2008;109(4):c192-7. Epub 2008 Sep 18. Read Abstract.

Technology

  • Maherali N, Ahfeldt T, Rigamonti A, Utikal J, Cowan C, Hochedlinger K. A high-efficiency system for the generation and study of human induced pluripotent stem cells. Cell Stem Cell. 2008 Sep 11;3(3):340-5. Read Abstract.