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Research Newsletter - July 2008

Spotlight

This month's spotlighted article, published in the journal Nature, is by HSCI Principal Faculty members William T. Pu, MD of Children's Hospital Boston and Sean Wu, MD, PhD and Kenneth R. Chien, MD, PhD of Massachusetts General Hospital.

Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart

Abstract:

The heart is formed from cardiogenic progenitors expressing the transcription factors Nkx2-5 and Isl1 (refs 1 and 2). These multipotent progenitors give rise to cardiomyocyte, smooth muscle and endothelial cells, the major lineages of the mature heart. Here we identify a novel cardiogenic precursor marked by expression of the transcription factor Wt1 and located within the epicardium-an epithelial sheet overlying the heart. During normal murine heart development, a subset of these Wt1(+) precursors differentiated into fully functional cardiomyocytes. Wt1(+) proepicardial cells arose from progenitors that express Nkx2-5 and Isl1, suggesting that they share a developmental origin with multipotent Nkx2-5(+) and Isl1(+) progenitors. These results identify Wt1(+) epicardial cells as previously unrecognized cardiomyocyte progenitors, and lay the foundation for future efforts to harness the cardiogenic potential of these progenitors for cardiac regeneration and repair.

Zhou B, Ma Q, Rajagopal S, Wu SM, Domian I, Rivera-Feliciano J, Jiang D, von Gise A, Ikeda S, Chien KR, Pu WT. Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature. 2008 Jun 22. Read Paper.

Scientific Papers

Review and Commentary

  • Faber J, Gregory RI, Armstrong SA. Linking miRNA regulation to BCR-ABL expression: the next dimension. Cancer Cell. 2008 Jun;13(6):467-9. Read Abstract.
  • Korngold EC, Jaffer FA, Weissleder R, Sosnovik DE. Noninvasive imaging of apoptosis in cardiovascular disease. Heart Fail Rev. 2008 Jun;13(2):163-73. Read Abstract.
  • Traum AZ, Kawai T, Vacanti JP, Sachs DH, Cosimi AB, Madsen JC. The need for tolerance in pediatric organ transplantation. Pediatrics. 2008 Jun;121(6):1258-60. Read Abstract.
  • Woods IG, Schier AF. Targeted mutagenesis in zebrafish. Nat Biotechnol. 2008 Jun;26(6):650-1. Read Abstract.
  • Zon LI. Self-renewal and differentiation at Cell Stem Cell. Cell Stem Cell. 2008 Jun 5;2(6):510. Read Abstract.

Blood

  • Armistead PM, Mohseni M, Gerwin R, Walsh EC, Iravani M, Chahardouli B, Rostami S, Zhang W, Neuberg D, Rioux J, Ghavamzadeh A, Ritz J, Antin JH, Wu CJ. Erythroid-lineage-specific engraftment in patients with severe hemoglobinopathy following allogeneic hematopoietic stem cell transplantation. Exp Hematol. 2008 Jun 10. Read Abstract.
  • Dooley KA, Fraenkel PG, Langer NB, Schmid B, Davidson AJ, Weber G, Chiang K, Foott H, Dwyer C, Wingert RA, Zhou Y, Paw BH, Zon LI. T√ɬºbingen 2000 Screen Consortium. montalcino, A zebrafish model for variegate porphyria. Exp Hematol. 2008 Jun 10. Read Abstract.
  • Guo F, Cancelas JA, Hildeman D, Williams DA, Zheng Y. Rac GTPase isoforms, Rac1 and Rac2, play a redundant and crucial role in T-cell development. Blood. 2008 Jun 25. Read Abstract.
  • Janzen V, Fleming HE, Riedt T, Karlsson G, Riese MJ, Lo Celso C, Reynolds G, Milne CD, Paige CJ, Karlsson S, Woo M, Scadden DT. Hematopoietic stem cell responsiveness to exogenous signals is limited by caspase-3. Cell Stem Cell. 2008 Jun 5;2(6):584-94. Read Abstract.
  • Wang Y, Yabuuchi A, McKinney-Freeman S, Ducharme DM, Ray MK, Chawengsaksophak K, Archer TK, Daley GQ. Cdx gene deficiency compromises embryonic hematopoiesis in the mouse. Proc Natl Acad Sci USA. 2008 Jun 3;105(22):7756-61. Epub 2008 May 29. Read Abstract.
  • Zhang X, Shang X, Guo F, Murphy K, Kirby M, Kelly P, Reeves L, Smith FO, Williams DA, Zheng Y, Pang Q. Defective homing is associated with altered Cdc42 activity in cells from Fanconi anemia group A patients. Blood. 2008 Jun 18. Read Abstract.

Cancer

  • Scaglioni PP, Yung TM, Choi SC, Baldini C, Konstantinidou G, Pandolfi PP. CK2 mediates phosphorylation and ubiquitin-mediated degradation of the PML tumor suppressor. Mol Cell Biochem. 2008 Jun 20. Read Abstract.
  • Tam WF, Gu TL, Chen J, Lee BH, Bullinger L, Frohling S, Wang A, Monti S, Golub TR, Gilliland DG. Id1 is a common downstream target of oncogenic tyrosine kinases in leukemic cells. Blood. 2008 Jun 17. Read Abstract.
  • Walkley CR, Qudsi R, Sankaran VG, Perry JA, Gostissa M, Roth SI, Rodda SJ, Snay E, Dunning P, Fahey FH, Alt FW, McMahon AP, Orkin SH. Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease. Genes Dev. 2008 Jun 15;22(12):1662-1676. Read Abstract.
  • Yamada Y, Sanchez-Aguilera A, Brandt EB, McBride M, Al-Moamen NJ, Finkelman FD, Williams DA, Cancelas JA, Rothenberg ME. FIP1L1/PDGFR{alpha} synergizes with SCF to induce systemic mastocytosis in a murine model of chronic eosinophilic leukemia/hypereosinophilic syndrome. Blood. 2008 Jun 6. Read Abstract.

Cardiovascular System

  • Adams JW, Wang J, Davis JR, Liaw C, Gaidarov I, Gatlin J, Dalton ND, Gu Y, Ross Jr JR, Behan D, Chien KR, Connolly D. Myocardial expression, signaling, and function of GPR22; A protective role for an orphan G-protein coupled receptor. Am J Physiol Heart Circ Physiol. 2008 Jun 6. Read Abstract.
  • Geier C, Gehmlich K, Ehler E, Hassfeld S, Perrot A, Hayess K, Cardim N, Wenzel K, Erdmann B, Krackhardt F, Posch MG, Bublak A, N√ɬ§gele H, Scheffold T, Dietz R, Chien KR, Spuler S, F√ɬºrst DO, N√ɬºrnberg P, Ozcelik C. Beyond the sarcomere: CSRP3 mutations cause hypertrophic cardiomyopathy. Hum Mol Genet. 2008 Jun 2. Read Abstract.
  • Zhou B, Ma Q, Rajagopal S, Wu SM, Domian I, Rivera-Feliciano J, Jiang D, von Gise A, Ikeda S, Chien KR, Pu WT. Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature. 2008 Jun 22. Read Abstract.

Developmental Biology

  • Lu CW, Yabuuchi A, Chen L, Viswanathan S, Kim K, Daley GQ. Ras-MAPK signaling promotes trophectoderm formation from embryonic stem cells and mouse embryos. Nat Genet. 2008 Jul;40(7):921-6. Epub 2008 Jun 8. Read Abstract.
  • Lu J, Guo S, Ebert BL, Zhang H, Peng X, Bosco J, Pretz J, Schlanger R, Wang JY, Mak RH, Dombkowski DM, Preffer FI, Scadden DT, Golub TR. MicroRNA-mediated control of cell fate in megakaryocyte-erythrocyte progenitors. Dev Cell. 2008 Jun;14(6):843-53. Read Abstract.
  • Piskounova E, Viswanathan SR, Janas M, Lapierre RJ, Daley GQ, Sliz P, Gregory RI. Determinants of microRNA processing inhibition by the developmentally regulated RNA-binding protein Lin28. J Biol Chem. 2008 Jun 12. Read Abstract.

Diabetes

  • Bonner-Weir S, Inada A, Yatoh S, Li WC, Aye T, Toschi E, Sharma A. Transdifferentiation of pancreatic ductal cells to endocrine beta-cells. Biochem Soc Trans. 2008 Jun;36(Pt 3):353-6. Read Abstract.
  • Butty V, Campbell C, Mathis D, Benoist C; the Diabetes Prevention Trial-Type 1 Study Group. Impact of diabetes susceptibility loci on progression from pre-diabetes to diabetes in at-risk individuals of the DPT1 trial. Diabetes. 2008 Jun 12. Read Abstract.

Imaging

  • Farrar CT, Dai G, Novikov M, Rosenzweig A, Weissleder R, Rosen BR, Sosnovik DE. Impact of field strength and iron oxide nanoparticle concentration on the linearity and diagnostic accuracy of off-resonance imaging. NMR Biomed. 2008 Jun;21(5):453-63. Read Abstract.
  • Taktak S, Weissleder R, Josephson L. Electrode Chemistry Yields a Nanoparticle-Based NMR Sensor for Calcium. Langmuir. 2008 Jun 18. Read Abstract.

Immunology

  • Johnsen AK, Plenge RM, Butty V, Campbell C, Dieguez-Gonzalez R, Gomez-Reino JJ, Shadick N, Weinblatt M, Gonzalez A, Gregersen PK, Benoist C, Mathis D. A broad analysis of IL1 polymorphism and rheumatoid arthritis. Arthritis Rheum. 2008 Jun 24;58(7):1947-1957. Read Abstract.
  • Sama MA, Mathis DM, Furman JL, Mohmmad Abdul H, Artiushin IA, Kraner SD, Norris CM. Interleukin-1beta -dependent signaling between astrocytes and neurons depends critically on astrocytic calcineurin/nfat activity. J Biol Chem. 2008 Jun 9. Read Abstract.

Nervous System

  • de Chevigny A, Cooper O, Vinuela A, Reske-Nielsen C, Lagace DC, Eisch AJ, Isacson O. Fate Mapping and Lineage Analyses Demonstrate the Production of a Large Number of Striatal Neuroblasts after TGF{alpha} and Noggin Striatal Infusions into the Dopamine-depleted Striatum. Stem Cells. 2008 Jun 12. Read Abstract.
  • Rodino-Klapac LR, Lee JS, Mulligan RC, Clark KR, Mendell JR. Lack of toxicity of alpha-sarcoglycan overexpression supports clinical gene transfer trial in LGMD2D. Neurology. 2008 Jun 18. Read Abstract.
  • Taylor AL, Bonventre JV, Uliasz TF, Hewett JA, Hewett SJ. Cytosolic Phospholipase A(2)alpha Inhibition Prevents Neuronal NMDA Receptor-Stimulated Arachidonic Acid Mobilization and Prostaglandin Production but not Subsequent Cell Death. J Neurochem. 2008 Jun 17. Read Abstract.

Technology

  • Huangfu D, Maehr R, Guo W, Eijkelenboom A, Snitow M, Chen AE, Melton DA. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol. 2008 Jun 22. Read Abstract.

Tissue Engineering

  • Steigman SA, Armant M, Bayer-Zwirello L, Kao GS, Silberstein L, Ritz J, Fauza DO. Preclinical regulatory validation of a 3-stage amniotic mesenchymal stem cell manufacturing protocol. J Pediatr Surg. 2008 Jun;43(6):1164-9. Read Abstract.