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Research Newsletter - November 2008

Spotlight

In an article paper published in Nature Biotechnology, HSCI Co-Director Douglas Melton, postdoctoral fellow Danwei Huangfu, and colleagues report the induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2.

Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2

Abstract:

Ectopic expression of defined sets of genetic factors can reprogram somatic cells to induced pluripotent stem (iPS) cells that closely resemble embryonic stem (ES) cells. The low efficiency with which iPS cells are derived hinders studies on the molecular mechanism of reprogramming, and integration of viral transgenes, in particular the oncogenes c-Myc and Klf4, may handicap this method for human therapeutic applications. Here we report that valproic acid (VPA), a histone deacetylase inhibitor, enables reprogramming of primary human fibroblasts with only two factors, Oct4 and Sox2, without the need for the oncogenes c-Myc or Klf4. The two factor-induced human iPS cells resemble human ES cells in pluripotency, global gene expression profiles and epigenetic states. These results support the possibility of reprogramming through purely chemical means, which would make therapeutic use of reprogrammed cells safer and more practical.

Huangfu D, Osafune K, Maehr R, Guo W, Eijkelenboom A, Chen S, Muhlestein W, Melton DA. Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat Biotechnol. 2008 Nov;26(11):1269-75. Epub 2008 Oct 12. Read Paper.

Scientific Papers

Review and Commentary

  • Bernardi R, Papa A, Pandolfi PP. Regulation of apoptosis by PML and the PML-NBs. Oncogene. 2008 Oct 30;27(48):6299-312. Read Abstract.
  • Blackwell TK, Walker AK. OMA-gosh, where's that TAF? Cell. 2008 Oct 3;135(1):18-20. Read Abstract.
  • Gazit R, Weissman IL, Rossi DJ. Hematopoietic stem cells and the aging hematopoietic system. Semin Hematol. 2008 Oct;45(4):218-24. Read Abstract.
  • Hoenig MR, Bianchi C, Rosenzweig A, Sellke FW. The cardiac microvasculature in hypertension, cardiac hypertrophy and diastolic heart failure. Curr Vasc Pharmacol. 2008 Oct;6(4):292-300. Review. Read Abstract.
  • Kalaitzidis D, Gilliland DG. Going with the flow: JAK-STAT signaling in JMML. Cancer Cell. 2008 Oct 7;14(4):279-80. Read Abstract.
  • Walsh CA, Morrow EM, Rubenstein JL. Autism and brain development. Cell. 2008 Oct 31;135(3):396-400. Read Abstract.
  • Zhou Q, Melton DA. Extreme makeover: converting one cell into another. Cell Stem Cell. 2008 Oct 9;3(4):382-8. Read Abstract.

Blood

  • Imamura S, Uchiyama J, Koshimizu E, Hanai J, Raftopoulou C, Murphey RD, Bayliss PE, Imai Y, Burns CE, Masutomi K, Gagos S, Zon LI, Roberts TM, Kishi S. A non-canonical function of zebrafish telomerase reverse transcriptase is required for developmental hematopoiesis. PLoS ONE. 2008;3(10):e3364. Epub 2008 Oct 10. Read Abstract.
  • Rodrigues NP, Boyd AS, Fugazza C, May GE, Guo Y, Tipping AJ, Scadden DT, Vyas P, Enver T. GATA-2 regulates granulocyte-macrophage progenitor cell function. Blood. 2008 Oct 7. Read Abstract.

Cancer

  • George RE, Sanda T, Hanna M, Fr√ɬ∂hling S, Luther W 2nd, Zhang J, Ahn Y, Zhou W, London WB, McGrady P, Xue L, Zozulya S, Gregor VE, Webb TR, Gray NS, Gilliland DG, Diller L, Greulich H, Morris SW, Meyerson M, Look AT. Activating mutations in ALK provide a therapeutic target in neuroblastoma. Nature. 2008 Oct 16;455(7215):975-8. Read Abstract.
  • Girnun GD, Chen L, Silvaggi J, Drapkin R, Chirieac LR, Padera RF, Upadhyay R, Vafai SB, Weissleder R, Mahmood U, Naseri E, Buckley S, Li D, Force J, McNamara K, Demetri G, Spiegelman BM, Wong KK. Regression of drug-resistant lung cancer by the combination of rosiglitazone and carboplatin. Clin Cancer Res. 2008 Oct 15;14(20):6478-86. Read Abstract.
  • Stone RM, DeAngelo DJ, Janosova A, Galinsky I, Canning C, Ritz J, Soiffer RJ. Low dose interleukin-2 following intensification therapy with high dose cytarabine for acute myelogenous leukemia in first complete remission. Am J Hematol. 2008 Oct;83(10):771-7. Read Abstract.

Cardiovascular System

  • Lewis GD, Wei R, Liu E, Yang E, Shi X, Martinovic M, Farrell L, Asnani A, Cyrille M, Ramanathan A, Shaham O, Berriz G, Lowry PA, Palacios IF, Ta√Ö≈∏an M, Roth FP, Min J, Baumgartner C, Keshishian H, Addona T, Mootha VK, Rosenzweig A, Carr SA, Fifer MA, Sabatine MS, Gerszten RE. Metabolite profiling of blood from individuals undergoing planned myocardial infarction reveals early markers of myocardial injury. J Clin Invest. 2008 Oct;118(10):3503-12. Read Abstract.
  • Mellgren AM, Smith CL, Olsen GS, Eskiocak B, Zhou B, Kazi MN, Ruiz FR, Pu WT, Tallquist MD. Platelet-Derived Growth Factor Receptor {beta} Signaling Is Required for Efficient Epicardial Cell Migration and Development of Two Distinct Coronary Vascular Smooth Muscle Cell Populations. Circ Res. 2008 Oct 23. 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

  • Chou YF, Chen HH, Eijpe M, Yabuuchi A, Chenoweth JG, Tesar P, Lu J, McKay RD, Geijsen N. The growth factor environment defines distinct pluripotent ground states in novel blastocyst-derived stem cells. Cell. 2008 Oct 31;135(3):449-61. Read Abstract.
  • Jinnin M, Medici D, Park L, Limaye N, Liu Y, Boscolo E, Bischoff J, Vikkula M, Boye E, Olsen BR. Suppressed NFAT-dependent VEGFR1 expression and constitutive VEGFR2 signaling in infantile hemangioma. Nat Med. 2008 Nov;14(11):1236-46. Epub 2008 Oct 19. Read Abstract.
  • Terranova R, Yokobayashi S, Stadler MB, Otte AP, van Lohuizen M, Orkin SH, Peters AH. Polycomb group proteins Ezh2 and Rnf2 direct genomic contraction and imprinted repression in early mouse embryos. Dev Cell. 2008 Nov;15(5):668-79. Epub 2008 Oct 9. Read Abstract.
  • Trimarchi JM, Harpavat S, Billings NA, Cepko CL. Thyroid hormone components are expressed in three sequential waves during development of the chick retina. BMC Dev Biol. 2008 Oct 14;8:101. Read Abstract.
  • Vokes SA, Ji H, Wong WH, McMahon AP. A genome-scale analysis of the cis-regulatory circuitry underlying sonic hedgehog-mediated patterning of the mammalian limb. Genes Dev. 2008 Oct 1;22(19):2651-63. 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.
  • Wu JY, Purton LE, Rodda SJ, Chen M, Weinstein LS, McMahon AP, Scadden DT, Kronenberg HM. Osteoblastic regulation of B lymphopoiesis is mediated by Gs{alpha}-dependent signaling pathways. Proc Natl Acad Sci USA. 2008 Nov 4;105(44):16976-81. Epub 2008 Oct 28. Read Abstract.

Diabetes

  • Akashi T, Shigematsu H, Hamamoto Y, Iwasaki H, Yatoh S, Bonner-Weir S, Akashi K, Weir GC. Bone marrow or foetal liver cells fail to induce islet regeneration in diabetic Akita mice. Diabetes Metab Res Rev. 2008 Oct;24(7):585-90. Read Abstract.
  • Koulmanda M, Bhasin M, Hoffman L, Fan Z, Qipo A, Shi H, Bonner-Weir S, Putheti P, Degauque N, Libermann TA, Auchincloss H Jr, Flier JS, Strom TB. Curative and beta cell regenerative effects of alpha1-antitrypsin treatment in autoimmune diabetic NOD mice. Proc Natl Acad Sci USA. 2008 Oct 21;105(42):16242-7. Epub 2008 Oct 13. Read Abstract.

Genetics and Genomics

  • Guyon JR, Goswami J, Jun SJ, Thorne M, Howell M, Pusack T, Kawahara G, Steffen LS, Galdzicki M, Kunkel LM. Genetic isolation and characterization of a splicing mutant of zebrafish dystrophin. Hum Mol Genet. 2008 Oct 28. Read Abstract.
  • Ku M, Koche RP, Rheinbay E, Mendenhall EM, Endoh M, Mikkelsen TS, Presser A, Nusbaum C, Xie X, Chi AS, Adli M, Kasif S, Ptaszek LM, Cowan CA, Lander ES, Koseki H, Bernstein BE. Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains. PLoS Genet. 2008 Oct;4(10):e1000242. Epub 2008 Oct 31. Read Abstract.

Imaging

  • Jaffer FA, Vinegoni C, John MC, Aikawa E, Gold HK, Finn AV, Ntziachristos V, Libby P, Weissleder R. Real-time catheter molecular sensing of inflammation in proteolytically active atherosclerosis. Circulation. 2008 Oct 28;118(18):1802-9. Epub 2008 Oct 13. Read Abstract.
  • Kim YR, Tejima E, Huang S, Atochin DN, Dai G, Lo EH, Huang PL, Bogdanov A Jr, Rosen BR. In vivo quantification of transvascular water exchange during the acute phase of permanent stroke. Magn Reson Med. 2008 Oct;60(4):813-21. Read Abstract.
  • Kozloff KM, Quinti L, Patntirapong S, Hauschka PV, Tung CH, Weissleder R, Mahmood U. Non-invasive optical detection of cathepsin K-mediated fluorescence reveals osteoclast activity in vitro and in vivo. Bone. 2008 Oct 22. Read Abstract.
  • Perez JM, Grimm J, Josephson L, Weissleder R. Integrated nanosensors to determine levels and functional activity of human telomerase. Neoplasia. 2008 Oct;10(10):1066-72. Read Abstract.

Immunology

  • Koh AS, Kuo AJ, Park SY, Cheung P, Abramson J, Bua D, Carney D, Shoelson SE, Gozani O, Kingston RE, Benoist C, Mathis D. Aire employs a histone-binding module to mediate immunological tolerance, linking chromatin regulation with organ-specific autoimmunity. Proc Natl Acad Sci USA. 2008 Oct 14;105(41):15878-83. Epub 2008 Oct 7. Read Abstract.
  • Venanzi ES, Melamed R, Mathis D, Benoist C. The variable immunological self: genetic variation and nongenetic noise in Aire-regulated transcription. Proc Natl Acad Sci USA. 2008 Oct 14;105(41):15860-5. Epub 2008 Oct 6. Read Abstract.
  • Villaseñor J, Besse W, Benoist C, Mathis D. Ectopic expression of peripheral-tissue antigens in the thymic epithelium: probabilistic, monoallelic, misinitiated. Proc Natl Acad Sci USA. 2008 Oct 14;105(41):15854-9. Epub 2008 Oct 3. Read Abstract.

Nervous System

  • Caron SJ, Prober D, Choy M, Schier AF. In vivo birthdating by BAPTISM reveals that trigeminal sensory neuron diversity depends on early neurogenesis. Development. 2008 Oct;135(19):3259-69. Epub 2008 Aug 28. Read Abstract.
  • Joshi PS, Molyneaux BJ, Feng L, Xie X, Macklis JD, Gan L. Bhlhb5 regulates the postmitotic acquisition of area identities in layers II-V of the developing neocortex. Neuron. 2008 Oct 23;60(2):258-72. Read Abstract.
  • Prober DA, Zimmerman S, Myers BR, McDermott BM Jr, Kim SH, Caron S, Rihel J, Solnica-Krezel L, Julius D, Hudspeth AJ, Schier AF. Zebrafish TRPA1 channels are required for chemosensation but not for thermosensation or mechanosensory hair cell function. J Neurosci. 2008 Oct 1;28(40):10102-10. Read Abstract.
  • Sanchez-Mejia RO, Newman JW, Toh S, Yu GQ, Zhou Y, Halabisky B, Ciss√ɬ© M, Scearce-Levie K, Cheng IH, Gan L, Palop JJ, Bonventre JV, Mucke L. Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer's disease. Nat Neurosci. 2008 Nov;11(11):1311-8. Epub 2008 Oct 19. Read Abstract.

Renal System

  • Ho J, Ng KH, Rosen S, Dostal A, Gregory RI, Kreidberg JA. Podocyte-specific loss of functional microRNAs leads to rapid glomerular and tubular injury. J Am Soc Nephrol. 2008 Nov;19(11):2069-75. Epub 2008 Oct 2. Read Abstract.
  • Kazama I, Mahoney Z, Miner JH, Graf D, Economides AN, Kreidberg JA. Podocyte-derived BMP7 is critical for nephron development. J Am Soc Nephrol. 2008 Nov;19(11):2181-91. Epub 2008 Oct 15. Read Abstract.
  • Zang ZJ, Gunaratnam L, Cheong JK, Lai LY, Hsiao LL, O'Leary E, Sun X, Salto-Tellez M, Bonventre JV, Hsu SI. Identification of PP2A as a novel interactor and regulator of TRIP-Br1. Cell Signal. 2008 Oct 7. Read Abstract.

Skeletal System

  • Aliprantis AO, Ueki Y, Sulyanto R, Park A, Sigrist KS, Sharma SM, Ostrowski MC, Olsen BR, Glimcher LH. NFATc1 in mice represses osteoprotegerin during osteoclastogenesis and dissociates systemic osteopenia from inflammation in cherubism. J Clin Invest. 2008 Nov 3;118(11):3775-3789. Epub 2008 Oct 9. Read Abstract.

Technology

  • Freeman JL, Ceol C, Feng H, Langenau DM, Belair C, Stern HM, Song A, Paw BH, Look AT, Zhou Y, Zon LI, Lee C. Construction and application of a zebrafish array comparative genomic hybridization platform. Genes Chromosomes Cancer. 2008 Oct 30. Read Abstract.
  • Garanger E, Aikawa E, Reynolds F, Weissleder R, Josephson L. Simplified syntheses of complex multifunctional nanomaterials. Chem Commun (Camb). 2008 Oct 21;(39):4792-4. Epub 2008 Aug 13. Read Abstract.
  • Huangfu D, Osafune K, Maehr R, Guo W, Eijkelenboom A, Chen S, Muhlestein W, Melton DA. Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat Biotechnol. 2008 Nov;26(11):1269-75. Epub 2008 Oct 12. Read Abstract.

Tissue Engineering

  • Bettinger CJ, Kulig KM, Vacanti JP, Langer R, Borenstein JT. Nanofabricated Collagen-Inspired Synthetic Elastomers for Primary Rat Hepatocyte Culture. Tissue Eng Part A. 2008 Oct 10. Read Abstract.
  • Zhang W, Abukawa H, Troulis MJ, Kaban LB, Vacanti JP, Yelick PC. Tissue engineered hybrid tooth-bone constructs. Methods. 2008 Oct 6. Read Abstract.