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Research Newsletter - December 2006

Spotlight

In two papers published in Cell, investigators from the Harvard Stem Cell Institute, Massachusetts General Hospital, and Childrens Hospital Boston describe how cloned progenitor cells can differentiate into cardiac muscle, smooth muscle, or endothelial cells.

Research reveals master heart cell

Cardiogenesis requires the generation of endothelial, cardiac, and smooth muscle cells, however the lineage of these cell types remains incompletely understood.

"The mechanism of cardiogenesis has fascinated biologists for two centuries," says Stuart Orkin, who led the team of researchers at Childrens Hospital Boston. "Despite beliefs that the different cells had distinct origins, recent animal experiments have suggested that a large proportion of cells in the mature heart share a common ancestry. To investigate this, we isolated cardiac progenitor cells from early stage mouse embryos and followed their differentiation. Expectedly, the majority of these cells differentiated spontaneously into muscle cells that expand and contract the heart's chambers. But, surprisingly, a subset of the cells adapted a smooth muscle cell fate." These results support the existence of a common precursor for cardiovascular lineages in the mammalian heart.

In a separate study, Kenneth Chien, director of the Harvard Stem Cell Institute's cardiovascular disease program and Massachusetts General Hospital's center for cardiovascular research, and his team used genetic fate-mapping studies to document that ES cell-derived multipotent isl1+ cardiovascular precursors can generate each of these diverse cardiovascular cell types in vivo.

"These progenitor cells offer new prospects for drug discovery and suggest a novel strategy for regeneration of cardiovascular tissue," says Chien. "The results suggest an alternative strategy for achieving the regeneration of distinct heart components that are affected in diverse forms of degenerative heart disease."

The next step will be to translate these findings in mouse models into human cells.

Moretti A, Caron L, Nakano A, Lam JT, Bernshausen A, Chen Y, Qyang Y, Bu L, Sasaki M, Martin-Puig S, Sun Y, Evans SM, Laugwitz KL, Chien KR. Multipotent Embryonic Isl1(+) Progenitor Cells Lead to Cardiac, Smooth Muscle, and Endothelial Cell Diversification. Cell. 2006 Nov 20; Read Abstract.

Wu SM, Fujiwara Y, Cibulsky SM, Clapham DE, Lien CL, Schultheiss TM, Orkin SH. Developmental Origin of a Bipotential Myocardial and Smooth Muscle Cell Precursor in the Mammalian Heart. Cell. 2006 Nov 20 Read Abstract.

Scientific Papers

Review and Commentary

  • Bonventre JV, Duffield JS. Response to 'Could tubular interstitium be a source of adult epithelial stem cells?' Kidney Int. 2006 Dec;70(11):2040-2041. Read Abstract.
  • Burns CE, Zon LI. Homing sweet homing: odyssey of hematopoietic stem cells. Immunity. 2006 Dec;25(6):859-62. Read Abstract.
  • Rubin LL, de Sauvage FJ. Targeting the Hedgehog pathway in cancer. Nat Rev Drug Discov. 2006 Dec;5(12):1026-33. Read Abstract.

Blood

  • Kelly KA, Allport JR, Yu AM, Sinh S, Sage EH, Gerszten RE, Weissleder R. SPARC is a VCAM-1 counter-ligand that mediates leukocyte transmigration. J Leukoc Biol. 2006 Dec 18. Read Abstract.
  • Lasho TL, Pardanani A, McClure RF, Mesa RA, Levine RL, Gilliland DG, Tefferi A. Concurrent MPL515 and JAK2V617F mutations in myelofibrosis: chronology of clonal emergence and changes in mutant allele burden over time. Br J Haematol. 2006 Dec;135(5):683-7. Read Abstract.

Cancer

  • Kobayashi S, Shimamura T, Monti S, Steidl U, Hetherington CJ, Lowell AM, Golub T, Meyerson M, Tenen DG, Shapiro GI, Halmos B. Transcriptional profiling identifies cyclin D1 as a critical downstream effector of mutant epidermal growth factor receptor signaling. Cancer Res. 2006 Dec 1;66(23):11389-98. Read Abstract.

Cardiovascular System

  • Feng Y, Chen MH, Moskowitz IP, Mendonza AM, Vidali L, Nakamura F, Kwiatkowski DJ, Walsh CA. Filamin A (FLNA) is required for cell-cell contact in vascular development and cardiac morphogenesis. Proc Natl Acad Sci USA. 2006 Dec 26;103(52):19836-41. Read Abstract.
  • Laustsen PG, Russell SJ, Cui L, Entingh-Pearsall A, Holzenberger M, Liao R, Kahn CR. Essential Role of Insulin and IGF-1 Receptor Signaling in Cardiac Development and Function. Mol Cell Biol. 2006 Dec 22. Read Abstract.

Developmental Biology

  • Bogunovic M, Ginhoux F, Wagers A, Loubeau M, Isola LM, Lubrano L, Najfeld V, Phelps RG, Grosskreutz C, Scigliano E, Frenette PS, Merad M. Identification of a radio-resistant and cycling dermal dendritic cell population in mice and men. J Exp Med. 2006 Nov 27;203(12):2627-38. Read Abstract.
  • Jadhav AP, Cho SH, Cepko CL. Notch activity permits retinal cells to progress through multiple progenitor states and acquire a stem cell property. Proc Natl Acad Sci USA. 2006 Dec 12;103(50):18998-9003. Read Abstract.
  • Kim K, Lerou P, Yabuuchi A, Lengerke C, Ng K, West J, Kirby A, Daly MJ, Daley GQ. Histocompatible Embryonic Stem Cells by Parthenogenesis. Science. 2006 Dec 14. Read Abstract.

Diabetes

  • Ahn YB, Xu G, Marselli L, Toschi E, Sharma A, Bonner-Weir S, Sgroi DC, Weir GC. Changes in gene expression in beta cells after islet isolation and transplantation using laser-capture microdissection. Diabetologia. 2006 Dec 16. Read Abstract.

Imaging

  • Grimm J, Kircher MF, Weissleder R. Cell tracking : Principles and applications. Radiologe. 2006 Dec 23. German. Read Abstract.
  • Izmailova ES, Paz N, Alencar H, Chun M, Schopf L, Hepperle M, Lane JH, Harriman G, Xu Y, Ocain T, Weissleder R, Mahmood U, Healy AM, Jaffee B. Use of molecular imaging to quantify response to IKK-2 inhibitor treatment in murine arthritis. Arthritis Rheum. 2006 Dec 28;56(1):117-128. Read Abstract.
  • Kim DE, Tsuji K, Kim YR, Mueller FJ, Eom HS, Snyder EY, Lo EH, Weissleder R, Schellingerhout D. Neural stem cell transplant survival in brains of mice: assessing the effect of immunity and ischemia by using real-time bioluminescent imaging. Radiology. 2006 Dec;241(3):822-30. Read Abstract.
  • Nahrendorf M, Weissleder R, Ertl G. Does FXIII Deficiency Impair Wound Healing after Myocardial Infarction? PLoS ONE. 2006 Dec 20;1:e48. Read Abstract.
  • Nahrendorf M, Weissleder R. Advances in cardiovascular medicine through molecular imaging. Radiologe. 2006 Dec 23. German. Read Abstract.
  • Saksena M, Harisinghani M, Hahn P, Kim J, Saokar A, King B, Weissleder R. Comparison of lymphotropic nanoparticle-enhanced MRI sequences in patients with various primary cancers. AJR Am J Roentgenol. 2006 Dec;187(6):W582-8. Read Abstract.

Immunology

  • Butty V, Roy M, Sabeti P, Besse W, Benoist C, Mathis D. Signatures of strong population differentiation shape extended haplotypes across the human CD28, CTLA4, and ICOS costimulatory genes. Proc Natl Acad Sci USA. 2006 Dec 29. Read Abstract.

Nervous System

  • Prober DA, Rihel J, Onah AA, Sung RJ, Schier AF. Hypocretin/orexin overexpression induces an insomnia-like phenotype in zebrafish. J Neurosci. 2006 Dec 20;26(51):13400-10. Read Abstract.

Pulmonary System

  • Ackerman KG, Wang J, Luo L, Fujiwara Y, Orkin SH, Beier DR. Gata4 is Necessary for Normal Pulmonary Lobar Development. Am J Respir Cell Mol Biol. 2006 Dec 1. Read Abstract.

Renal System

  • Perianayagam MC, Liangos O, Kolyada AY, Wald R, Mackinnon RW, Li L, Rao M, Balakrishnan VS, Bonventre JV, Pereira BJ, Jaber BL. NADPH Oxidase p22phox and Catalase Gene Variants Are Associated with Biomarkers of Oxidative Stress and Adverse Outcomes in Acute Renal Failure. J Am Soc Nephrol. 2007 Jan;18(1):255-263. Read Abstract.

Tissue Engineering

  • Hannouche D, Terai H, Fuchs JR, Terada S, Zand S, Nasseri BA, Petite H, Sedel L, Vacanti JP. Engineering of Implantable Cartilaginous Structures from Bone Marrow-Derived Mesenchymal Stem Cells. Tissue Eng. 2006 Dec 1. Read Abstract.