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This HSCI Research Update synthesizes the scientific work published by HSCI Principal Faculty each month. To continue receiving this newsletter, please register as an HSCI Affiliate or Friend by clicking here.
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In a paper published in Nature Methods, HSCI Imaging Program Leader Ralph Weissleder and a team of scientists at Massachusetts General Hospital describe a new method for visualizing living cells both in tissue culture and in animal models.
This method provides a new way for scientists to monitor cells, cell processes, and molecular targets. The team's work will play a critical role in advancing the field of stem cell research because scientists will be able to use the technique to help uncover the molecular and cellular details of stem cell development and differentiation.
"This is a powerful technique that can be broadly applied," said David Scadden, co-Scientific Director of HSCI. "It will allow researchers to track stem cell after they have been transferred into an animal model."
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In this technique, a reporter gene is transferred to the cells in question. A reporter gene is a piece of DNA that encodes a special reporter protein, which can then be tracked by a conjugate molecule. In this case, the reporter gene codes for a protein that first binds to biotin (vitamin H) and then moves to the surface of the cell.
Once this biotin-protein complex is present on the cell's surface, it can bind to the imaging agent. An imaging agent is a two-part molecule designed by the researcher for the purpose of visualization. When cells that have the biotin-protein complex on their surface are in the presence of the imaging agent, it binds to the biotin-protein complex and allows the cells to be seen.
This technique is versatile for two reasons. The first is that any type of cell can be made to express biotin on its surface by using the reporter gene. The second is that the imaging agent can be constructed using different types of signaling molecules. This provides researchers with multiple options for visualizing their cells - whether it be with fluorochromes, magnetic resonance, PET or SPECT agents.
Versatility is particularly important in stem cell research because the field involves so many different tissue and cell types. This paper provides researchers with a new method for tracking cells in a wide range of environments and models.
Tannous BA, Grimm J, Perry KF, Chen JW, Weissleder R, Breakefield XO. Metabolic biotinylation of cell surface receptors for in vivo imaging. Nat Methods. 2006 May;3(5):391-6. Read Abstract.
- Lensch MW, Daley GQ. (2006). Scientific and clinical opportunities for modeling blood disorders with embryonic stem cells. Blood. Apr 1;107(7):2605-12. Read Abstract.
- Adams GB, Scadden DT. (2006). The hematopoietic stem cell in its place. Nat Immunol. 2006 Apr;7(4):333-7. Read Abstract.
- Abukawa H, Papadaki M, Abulikemu M, Leaf J, Vacanti JP, Kaban LB, Troulis MJ. The engineering of craniofacial tissues in the laboratory: a review of biomaterials for scaffolds and implant coatings. Dent Clin North Am. 2006 Apr;50(2):205-16. Read Abstract.
- Weissleder R. Molecular imaging in cancer. Science. 2006 May 26;312(5777):1168-71. Read Abstract.
- Pabst T, Stillner E, Neuberg D, Nimer S, Willman CL, List AF, Melo JV, Tenen DG, Mueller BU. Mutations of the myeloid transcription factor CEBPA are not associated with the blast crisis of chronic myeloid leukaemia. Br J Haematol. 2006 May;133(4):400-2. Read Abstract.
- Rooke HM, Orkin SH. Phosphorylation of Gata1 at serine residues 72, 142, and 310 is not essential for hematopoiesis in vivo. Blood. 2006 May 1;107(9):3527-30. Read Abstract.
- Levine RL, Belisle C, Wadleigh M, Zahrieh D, Lee S, Chagnon P, Gilliland DG, Busque L. X-inactivation-based clonality analysis and quantitative JAK2V617F assessment reveal a strong association between clonality and JAK2V617F in PV but not ET/MMM, and identifies a subset of JAK2V617F-negative ET and MMM patients with clonal hematopoiesis. Blood. 2006 May 15;107(10):4139-41. Read Abstract.
- Guyot B, Murai K, Fujiwara Y, Valverde-Garduno V, Hammett M, Wells S, Dear N, Orkin SH, Porcher C, Vyas P. Characterization of a megakaryocyte-specific enhancer of the key hemopoietic transcription factor GATA1. J Biol Chem. 2006 May 12;281(19):13733-42. Read Abstract.
- Tefferi A, Barosi G, Mesa RA, Cervantes F, Deeg HJ, Reilly JT, Verstovsek S, Dupriez B, Silver RT, Odenike O, Cortes J, Wadleigh M, Solberg Jr LA, Camoriano JK, Gisslinger H, Noel P, Thiele J, Vardiman JW, Hoffman R, Cross NC, Gilliland DG, Kantarjian H. International Working Group (IWG) consensus criteria for treatment response in myelofibrosis with myeloid metaplasia: On behalf of the IWG for myelofibrosis research and treatment (IWG-MRT). Blood. 2006 May 4. Read Abstract.
- Chan IT, Kutok JL, Williams IR, Cohen S, Moore S, Shigematsu H, Ley TJ, Akashi K, Le Beau MM, Gilliland DG. Oncogenic K-ras cooperates with PML-RAR{alpha} to induce an acute promyelocytic leukemia-like disease. Blood. 2006 May 4. Read Abstract.
- Stover EH, Chen J, Folens C, Lee BH, Mentens N, Marynen P, Williams IR, Gilliland DG, Cools J. Activation of FIP1L1-PDGFR{alpha} requires disruption of the juxtamembrane domain of PDGFR{alpha} and is FIP1L1-independent. Proc Natl Acad Sci USA. 2006 May 23;103(21):8078-83. Read Abstract.
- Ji H, Li D, Chen L, Shimamura T, Kobayashi S, McNamara K, Mahmood U, Mitchell A, Sun Y, Al-Hashem R, Chirieac LR, Padera R, Bronson RT, Kim W, Janne PA, Shapiro GI, Tenen D, Johnson BE, Weissleder R, Sharpless NE, Wong KK. The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies. Cancer Cell. 2006 May 24. Read Abstract.
- Mueller BU, Pabst T, Hauser P, Gilliland G, Neuberg D, Tenen DG. Mutations of the transcription factor PU.1 are not associated with acute lymphoblastic leukaemia. Br J Cancer. 2006 May 30. Read Abstract.
- Yan CT, Kaushal D, Murphy M, Zhang Y, Datta A, Chen C, Monroe B, Mostoslavsky G, Coakley K, Gao Y, Mills KD, Fazeli AP, Tepsuporn S, Hall G, Mulligan R, Fox E, Bronson R, De Girolami U, Lee C, Alt FW. XRCC4 suppresses medulloblastomas with recurrent translocations in p53-deficient mice. Proc Natl Acad Sci USA. 2006 May 9;103(19):7378-83. Read Abstract.
- Certo M, Moore Vdel G, Nishino M, Wei G, Korsmeyer S, Armstrong SA, Letai A. Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. Cancer Cell. 2006 May;9(5):351-65. Read Abstract.
- Matsui T, Nagoshi T, Hong EG, Luptak I, Hartil K, Li L, Gorovits N, Charron MJ, Kim JK, Tian R, Rosenzweig A. Effects of chronic Akt activation on glucose uptake in the heart. Am J Physiol Endocrinol Metab. 2006 May;290(5):E789-97. Read Abstract.
- Gupta S, Zhu H, Zon LI, Evans T. BMP signaling restricts hemato-vascular development from lateral mesoderm during somitogenesis. Development. 2006 Jun;133(11):2177-87. Read Abstract.
- Pyati UJ, Cooper MS, Davidson AJ, Nechiporuk A, Kimelman D. Sustained Bmp signaling is essential for cloaca development in zebrafish. Development. 2006 Jun;133(11):2275-84. Read Abstract.
- Tenzen T, Allen BL, Cole F, Kang JS, Krauss RS, McMahon AP. The cell surface membrane proteins Cdo and Boc are components and targets of the Hedgehog signaling pathway and feedback network in mice. Dev Cell. 2006 May;10(5):647-56. Read Abstract.
- Goishi K, Shimizu A, Najarro G, Watanabe S, Rogers R, Zon LI, Klagsbrun M. {alpha}A-crystallin expression prevents {gamma}-crystallin insolubility and cataract formation in the zebrafish cloche mutant lens. Development. 2006 May 25. Read Abstract.
- Sherwood RI, Wagers AJ. Harnessing the potential of myogenic satellite cells. Trends Mol Med. 2006 May;12(5):189-92. Read Abstract.
- Lopez-Avalos MD, Duvivier-Kali VF, Xu G, Bonner-Weir S, Sharma A, Weir GC. Evidence for a role of the ubiquitin-proteasome pathway in pancreatic islets. Diabetes. 2006 May;55(5):1223-31. Read Abstract.
- Nishimura W, Kondo T, Salameh T, El Khattabi I, Dodge R, Bonner-Weir S, Sharma A. A switch from MafB to MafA expression accompanies differentiation to pancreatic beta-cells. Dev Biol. 2006 May 15;293(2):526-39. Read Abstract.
- Inada A, Nienaber C, Bonner-Weir S. Endogenous beta-galactosidase expression in murine pancreatic islets. Dev Biol. 2006 May;49(5):1120-2. Read Abstract.
- Mueller T, Terada T, Rosenberg IM, Shibolet O, Podolsky DK. Th2 Cytokines Down-Regulate TLR Expression and Function in Human Intestinal Epithelial Cells. J Immunol. 2006 May 15;176(10):5805-14. Read Abstract.
- Kelly KA, Nahrendorf M, Yu AM, Reynolds F, Weissleder R. In Vivo Phage Display Selection Yields Atherosclerotic Plaque Targeted Peptides for Imaging. Mol Imaging Biol. 2006 May 3. Read Abstract.
- Ho NH, Weissleder R, Tung CH. Development of a dual fluorogenic and chromogenic dipeptidyl peptidase IV substrate. Bioorg Med Chem Lett. 2006 May 15;16(10):2599-602. Read Abstract.
- Tannous BA, Grimm J, Perry KF, Chen JW, Weissleder R, Breakefield XO. Metabolic biotinylation of cell surface receptors for in vivo imaging. Nat Methods. 2006 May;3(5):391-6. Read Abstract.
- Montet X, Yuan H, Weissleder R, Josephson L. Enzyme-based visualization of receptor-ligand binding in tissues. Lab Invest. 2006 May;86(5):517-25. Read Abstract.
- de Pooter RF, Schmitt TM, de la Pompa JL, Fujiwara Y, Orkin SH, Zuniga-Pflucker JC. Notch signaling requires GATA-2 to inhibit myelopoiesis from embryonic stem cells and primary hemopoietic progenitors. J Immunol. 2006 May 1;176(9):5267-75. Read Abstract.
- Kim J, Kil IS, Seok YM, Yang ES, Kim DK, Lim DG, Park JW, Bonventre JV, Park KM. Orchiectomy attenuates post-ischemic oxidative stress and ischemia/reperfusion injury In mice. A role for manganese superoxide dismutase. J Biol Chem. 2006 May 8. Read Abstract.
- Sheen VL, Ferland RJ, Neal J, Harney M, Hill RS, Banham A, Brown P, Chenn A, Corbo J, Hecht J, Folkerth R, Walsh CA. Neocortical neuronal arrangement in Miller Dieker syndrome. Acta Neuropathol (Berl). 2006 May;111(5):489-96. Read Abstract.
- Parrini E, Ramazzotti A, Dobyns WB, Mei D, Moro F, Veggiotti P, Marini C, Brilstra EH, Bernardina BD, Goodwin L, Bodell A, Jones MC, Nangeroni M, Palmeri S, Said E, Sander JW, Striano P, Takahashi Y, Van Maldergem L, Leonardi G, Wright M, Walsh CA, Guerrini R. Periventricular heterotopia: phenotypic heterogeneity and correlation with Filamin A mutations. Brain. 2006 May 9. Read Abstract.
- Zhan Y, Fujino A, Maclaughlin DT, Manganaro TF, Szotek PP, Arango NA, Teixeira J, Donahoe PK. Mullerian inhibiting substance regulates its receptor/SMAD signaling and causes mesenchymal transition of the coelomic epithelial cells early in Mullerian duct regression. Development. 2006 Jun;133(12):2359-69. Read Abstract.
- Clark RA, Chong BF, Mirchandani N, Yamanaka K, Murphy GF, Dowgiert RK, Kupper TS. A novel method for the isolation of skin resident T cells from normal and diseased human skin. J Invest Dermatol. 2006 May;126(5):1059-70. Read Abstract.
- Yu J, McMahon AP. Reproducible and inducible knockdown of gene expression in mice. Genesis. 2006 May;44(5):252-61. Read Abstract.
- Yen L, Magnier M, Weissleder R, Stockwell BR, Mulligan RC. Identification of inhibitors of ribozyme self-cleavage in mammalian cells via high-throughput screening of chemical libraries. RNA. 2006 May;12(5):797-806. Read Abstract.
- Wu CJ, Ritz J. Induction of tumor immunity following allogeneic stem cell transplantation. Adv Immunol. 2006;90,133-73. Read Abstract.
The Harvard Stem Cell Institute is a scientific collaborative established to fulfill the promise of stem cell biology as the basis for cures and treatments for a wide range of chronic medical conditions.
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