Research Newsletter - September 2009

Spotlight

In an article paper published in Proceedings of the National Academy of Sciences, HSCI Co-Director Douglas Melton, PhD, and colleagues report he creation of induced pluripotent cells (iPS) cells from diabetes patients.

Generation of pluripotent stem cells from patients with type 1 diabetes

Abstract:

Type 1 diabetes (T1D) is the result of an autoimmune destruction of pancreatic beta cells. The cellular and molecular defects that cause the disease remain unknown. Pluripotent cells generated from patients with T1D would be useful for disease modeling. We show here that induced pluripotent stem (iPS) cells can be generated from patients with T1D by reprogramming their adult fibroblasts with three transcription factors (OCT4, SOX2, KLF4). T1D-specific iPS cells, termed DiPS cells, have the hallmarks of pluripotency and can be differentiated into insulin-producing cells. These results are a step toward using DiPS cells in T1D disease modeling, as well as for cell replacement therapy.

Maehr R, Chen S, Snitow M, Ludwig T, Yagasaki L, Goland R, Leibel RL, Melton DA. Generation of pluripotent stem cells from patients with type 1 diabetes. Proc Natl Acad Sci USA. 2009 Aug 31. [Epub ahead of print] Read Paper.

Scientific Papers

Review and Commentary

  • Cheung KJ, Ebert BL. Therapeutic potential of targeting haploinsufficient genes in cancer. Pediatr Blood Cancer. 2009 Aug;53(2):131-2. Review.

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  • Huang PL. eNOS, metabolic syndrome and cardiovascular disease. Trends Endocrinol Metab. 2009 Aug;20(6):295-302. Epub 2009 Jul 31.

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  • Meissner A. Alexander Meissner: learning the reprogramming code. J Cell Biol. 2009 Aug 24;186(4):450-1.

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  • Snow JW, Orkin SH. Translational isoforms of FOG1 regulate GATA1-interacting complexes. J Biol Chem. 2009 Aug 4. [Epub ahead of print]

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  • Williams DA. Gene therapy continues to mature and to face challenges. Mol Ther. 2009 Aug;17(8):1305-6.

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  • Zhao W, Karp JM. Controlling Cell Fate In Vivo. Chembiochem. 2009 Aug 11. [Epub ahead of print]

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Blood

  • Beekman JM, Verhagen LP, Geijsen N, Coffer PJ. Regulation of myelopoiesis through syntenin-mediated modulation of IL-5 receptor output. Blood. 2009 Aug 4. [Epub ahead of print]

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  • Eminli S, Foudi A, Stadtfeld M, Maherali N, Ahfeldt T, Mostoslavsky G, Hock H, Hochedlinger K. Differentiation stage determines potential of hematopoietic cells for reprogramming into induced pluripotent stem cells. Nat Genet. 2009 Sep;41(9):968-76. Epub 2009 Aug 9.

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  • Xu H, Eleswarapu S, Geiger H, Szczur K, Daria D, Zheng Y, Settleman J, Srour EF, Williams DA, Filippi MD. Loss of the Rho GTPase activating protein p190-B enhances hematopoietic stem cell engraftment potential. Blood. 2009 Aug 27. [Epub ahead of print]

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Cancer

  • Chen Z, Carracedo A, Lin HK, Koutcher JA, Behrendt N, Egia A, Alimonti A, Carver BS, Gerald W, Teruya-Feldstein J, Loda M, Pandolfi PP. Differential p53-independent outcomes of p19(Arf) loss in oncogenesis. Sci Signal. 2009 Aug 18;2(84):ra44.

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  • Cheng K, Sportoletti P, Ito K, Clohessy JG, Teruya-Feldstein J, Kutok JL, Pandolfi PP. The cytoplasmic NPM mutant induces myeloproliferation in a transgenic mouse model. Blood. 2009 Aug 7. [Epub ahead of print]

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  • Coser KR, Wittner BS, Rosenthal NF, Collins SC, Melas A, Smith SL, Mahoney CJ, Shioda K, Isselbacher KJ, Ramaswamy S, Shioda T. Antiestrogen-resistant subclones of MCF-7 human breast cancer cells are derived from a common monoclonal drug-resistant progenitor. Proc Natl Acad Sci USA. 2009 Aug 25;106(34):14536-41.

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  • Gewinner C, Wang ZC, Richardson A, Teruya-Feldstein J, Etemadmoghadam D, Bowtell D, Barretina J, Lin WM, Rameh L, Salmena L, Pandolfi PP, Cantley LC. Evidence that inositol polyphosphate 4-phosphatase type II is a tumor suppressor that inhibits PI3K signaling. Cancer Cell. 2009 Aug 4;16(2):115-25.

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  • Ho VT, Vanneman M, Kim H, Sasada T, Kag YJ, Pasek M, Cutler C, Koreth J, Alyea E, Sarantopoulos S, Antin JH, Ritz J, Canning C, Kutok J, Mihm MC, Dranoff G, Soiffer R. Biologic activity of irradiated, autologous, GM-CSF-secreting leukemia cell vaccines early after allogeneic stem cell transplantation. Proc Natl Acad Sci USA. 2009 Aug 26. [Epub ahead of print]

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  • Huang WS, Zhu X, Wang Y, Azam M, Wen D, Sundaramoorthi R, Thomas RM, Liu S, Banda G, Lentini SP, Das S, Xu Q, Keats J, Wang F, Wardwell S, Ning Y, Snodgrass JT, Broudy MI, Russian K, Daley GQ, Iuliucci J, Dalgarno DC, Clackson T, Sawyer TK, Shakespeare WC. 9-(Arenethenyl)purines as dual Src/Abl kinase inhibitors targeting the inactive conformation: design, synthesis, and biological evaluation. J Med Chem. 2009 Aug 13;52(15):4743-56.

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  • Yu M, Smolen GA, Zhang J, Wittner B, Schott BJ, Brachtel E, Ramaswamy S, Maheswaran S, Haber DA. A developmentally regulated inducer of EMT, LBX1, contributes to breast cancer progression. Genes Dev. 2009 Aug 1;23(15):1737-42.

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Cardiovascular System

  • An X, Jin Y, Guo H, Foo SY, Cully BL, Wu J, Zeng H, Rosenzweig A, Li J. Response gene to complement 32, a novel hypoxia-regulated angiogenic inhibitor. Circulation. 2009 Aug 18;120(7):617-27. Epub 2009 Aug 3.

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  • Das S, Makino S, Melman YF, Shea MA, Goyal SB, Rosenzweig A, Macrae CA, Ellinor PT. Mutation in the S3 segment of KCNQ1 results in familial lone atrial fibrillation. Heart Rhythm. 2009 Aug;6(8):1146-53. Epub 2009 Apr 15.

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  • Foo SY, Heller ER, Wykrzykowska J, Sullivan CJ, Manning-Tobin JJ, Moore KJ, Gerszten RE, Rosenzweig A. Vascular effects of a low-carbohydrate high-protein diet. Proc Natl Acad Sci USA. 2009 Aug 24. [Epub ahead of print]

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  • Rao PK, Toyama Y, Chiang HR, Gupta S, Bauer M, Medvid R, Reinhardt F, Liao R, Krieger M, Jaenisch R, Lodish HF, Blelloch R. Loss of cardiac microRNA-mediated regulation leads to dilated cardiomyopathy and heart failure. Circ Res. 2009 Sep 11;105(6):585-94. Epub 2009 Aug 13.

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Developmental Biology

  • Egli D, Sandler VM, Shinohara ML, Cantor H, Eggan K. Reprogramming after chromosome transfer into mouse blastomeres. Curr Biol. 2009 Aug 25;19(16):1403-9. Epub 2009 Aug 13.

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  • Sankaran VG, Xu J, Ragoczy T, Ippolito GC, Walkley CR, Maika SD, Fujiwara Y, Ito M, Groudine M, Bender MA, Tucker PW, Orkin SH. Developmental and species-divergent globin switching are driven by BCL11A. Nature. 2009 Aug 27;460(7259):1093-7. Epub 2009 Aug 5.

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  • Utikal J, Polo JM, Stadtfeld M, Maherali N, Kulalert W, Walsh RM, Khalil A, Rheinwald JG, Hochedlinger K. Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature. 2009 Aug 27;460(7259):1145-8. Epub 2009 Aug 9.

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Diabetes

  • Borowiec M, Liew CW, Thompson R, Boonyasrisawat W, Hu J, Mlynarski WM, El Khattabi I, Kim SH, Marselli L, Rich SS, Krolewski AS, Bonner-Weir S, Sharma A, Sale M, Mychaleckyj JC, Kulkarni RN, Doria A. Mutations at the BLK locus linked to maturity onset diabetes of the young and beta-cell dysfunction. Proc Natl Acad Sci USA. 2009 Aug 25;106(34):14460-5. Epub 2009 Aug 10.

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  • Maehr R, Chen S, Snitow M, Ludwig T, Yagasaki L, Goland R, Leibel RL, Melton DA. Generation of pluripotent stem cells from patients with type 1 diabetes. Proc Natl Acad Sci USA. 2009 Aug 31. [Epub ahead of print]

    Read Abstract.

Imaging

  • Garanger E, Hilderbrand SA, Blois JT, Sosnovik DE, Weissleder R, Josephson L. A DNA-binding Gd chelate for the detection of cell death by MRI. Chem Commun (Camb). 2009 Aug 7;(29):4444-6. Epub 2009 Jun 12.

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  • Rajendran R, Ronald JA, Ye T, Minqin R, Chen JW, Weissleder R, Rutt BK, Halliwell B, Watt F. Nuclear microscopy: a novel technique for quantitative imaging of gadolinium distribution within tissue sections. Microsc Microanal. 2009 Aug;15(4):338-44.

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  • Ronald JA, Chen JW, Chen Y, Hamilton AM, Rodriguez E, Reynolds F, Hegele RA, Rogers KA, Querol M, Bogdanov A, Weissleder R, Rutt BK. Enzyme-sensitive magnetic resonance imaging targeting myeloperoxidase identifies active inflammation in experimental rabbit atherosclerotic plaques. Circulation. 2009 Aug 18;120(7):592-9. Epub 2009 Aug 3.

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  • Vinegoni C, Razansky D, Pitsouli C, Perrimon N, Ntziachristos V, Weissleder R. Mesoscopic fluorescence tomography for in-vivo imaging of developing Drosophila. J Vis Exp. 2009 Aug 20;(30). pii: 1510. doi: 10.3791/1510.

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  • Vonken EJ, Korosoglou G, Yu J, Schär M, Weissleder R, Stuber M. On the dual contrast enhancement mechanism in frequency-selective inversion-recovery magnetic resonance angiography (IRON-MRA). Magn Reson Med. 2009 Aug;62(2):314-24.

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Immunology

  • Koreth J, Stevenson KE, Kim HT, Garcia M, Ho VT, Armand P, Cutler C, Ritz J, Antin JH, Soiffer RJ, Alyea EP 3rd. Bortezomib, tacrolimus and methotrexate for prophylaxis of graft-versus-host-disease after reduced-intensity conditioning allogeneic stem cell transplantation from HLA-mismatched unrelated donors. Blood. 2009 Aug 27. [Epub ahead of print]

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  • Monach PA, Hueber W, Kessler B, Tomooka BH, Benbarak M, Simmons BP, Wright J, Thornhill TS, Monestier M, Ploegh H, Robinson WH, Mathis D, Benoist C. A broad screen for targets of immune complexes decorating arthritic joints highlights deposition of nucleosomes in rheumatoid arthritis. Proc Natl Acad Sci USA. 2009 Aug 31. [Epub ahead of print]

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  • Stangenberg L, Ellson C, Cortez-Retamozo V, Ortiz-Lopez A, Yuan H, Blois J, Smith RA, Yaffe MB, Weissleder R, Benoist C, Mathis D, Josephson L, Mahmood U. Abrogation of antibody-induced arthritis in mice by a self-activating viridin prodrug and association with impaired neutrophil and endothelial cell function. Arthritis Rheum. 2009 Aug;60(8):2314-24.

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Molecular Biology

  • Gebauer JM, Keene DR, Olsen BR, Sorokin LM, Paulsson M, Wagener R. Mouse AMACO, a kidney and skin basement membrane associated molecule that mediates RGD-dependent cell attachment. Matrix Biol. 2009 Aug 3. [Epub ahead of print]

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  • Hagan JP, Piskounova E, Gregory RI. Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells. Nat Struct Mol Biol. 2009 Aug 27. [Epub ahead of print]

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  • Minamishima YA, Moslehi J, Padera RF, Bronson RT, Liao R, Kaelin WG Jr. A Feedback Loop Involving the Phd3 Prolyl Hydroxylase Tunes the Mammalian Hypoxic Response In Vivo. Mol Cell Biol. 2009 Aug 31. [Epub ahead of print]

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  • Schleicher M, Yu J, Murata T, Derakhshan B, Atochin D, Qian L, Kashiwagi S, Di Lorenzo A, Harrison KD, Huang PL, Sessa WC. The Akt1-eNOS axis illustrates the specificity of kinase-substrate relationships in vivo. Sci Signal. 2009 Aug 4;2(82):ra41.

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  • Xiong JP, Mahalingham B, Alonso JL, Borrelli LA, Rui X, Anand S, Hyman BT, Rysiok T, Müller-Pompalla D, Goodman SL, Arnaout MA. Crystal structure of the complete integrin alphaVbeta3 ectodomain plus an alpha/beta transmembrane fragment. J Cell Biol. 2009 Aug 24;186(4):589-600.

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Nervous System

  • Azim E, Jabaudon D, Fame RM, Macklis JD. SOX6 controls dorsal progenitor identity and interneuron diversity during neocortical development. Nat NeurosciM. 2009 Aug 5. [Epub ahead of print]

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  • Cooper O, Astradsson A, Hallett P, Robertson H, Mendez I, Isacson O. Lack of functional relevance of isolated cell damage in transplants of Parkinson's disease patients. J Neurol. 2009 Aug;256 Suppl 3:310-6.

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Technology

  • Robarge KD, Brunton SA, Castanedo GM, Cui Y, Dina MS, Goldsmith R, Gould SE, Guichert O, Gunzner JL, Halladay J, Jia W, Khojasteh C, Koehler MF, Kotkow K, La H, Lalonde RL, Lau K, Lee L, Marshall D, Marsters JC Jr, Murray LJ, Qian C, Rubin LL, Salphati L, Stanley MS, Stibbard JH, Sutherlin DP, Ubhayaker S, Wang S, Wong S, Xie M. GDC-0449-a potent inhibitor of the hedgehog pathway. Bioorg Med Chem Lett. 2009 Oct 1;19(19):5576-81. Epub 2009 Aug 15.

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