Research Newsletter - July 2009
Spotlight
In an article paper published in Nature, HSCI Executive Committee Member George Daley, MD, PhD, and colleagues show that bone-marrow adipocytes act as negative regulators of the haematopoietic microenvironment.
Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment
Abstract:
Osteoblasts and endothelium constitute functional niches that support haematopoietic stem cells in mammalian bone marrow. Adult bone marrow also contains adipocytes, the number of which correlates inversely with the haematopoietic activity of the marrow. Fatty infiltration of haematopoietic red marrow follows irradiation or chemotherapy and is a diagnostic feature in biopsies from patients with marrow aplasia. To explore whether adipocytes influence haematopoiesis or simply fill marrow space, we compared the haematopoietic activity of distinct regions of the mouse skeleton that differ in adiposity. Here we show, by flow cytometry, colony-forming activity and competitive repopulation assay, that haematopoietic stem cells and short-term progenitors are reduced in frequency in the adipocyte-rich vertebrae of the mouse tail relative to the adipocyte-free vertebrae of the thorax. In lipoatrophic A-ZIP/F1 'fatless' mice, which are genetically incapable of forming adipocytes, and in mice treated with the peroxisome proliferator-activated receptor-gamma inhibitor bisphenol A diglycidyl ether, which inhibits adipogenesis, marrow engraftment after irradiation is accelerated relative to wild-type or untreated mice. These data implicate adipocytes as predominantly negative regulators of the bone-marrow microenvironment, and indicate that antagonizing marrow adipogenesis may enhance haematopoietic recovery in clinical bone-marrow transplantation.
Naveiras O, Nardi V, Wenzel PL, Hauschka PV, Fahey F, Daley GQ. Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment. Nature. 2009 Jul 9;460(7252):259-63. Epub 2009 Jun 10. Read Paper.
Review and Commentary
Chen AT, Zon LI. Zebrafish blood stem cells. J Cell Biochem. 2009 Jun 29. [Epub ahead of print]
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Nathan DG, Orkin SH. Musings on genome medicine: cholesterol and coronary artery disease. Genome Med. 2009 Jun 8;1(6):60.
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Williams DA. Rapid development of pluripotent stem cells as a potential therapeutic modality. Mol Ther. 2009 Jun;17(6):929-30.
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Woolf CJ. Mu and delta opioid receptors diverge. Cell. 2009 Jun 12;137(6):987-8.
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Zhao W, Karp JM. Tumour targeting: Nanoantennas heat up. Nat Mater. 2009 Jun;8(6):453-4.
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Blood
Hofmann I, Stover EH, Cullen DE, Mao J, Morgan KJ, Lee BH, Kharas MG, Miller PG, Cornejo MG, Okabe R, Armstrong SA, Ghilardi N, Gould S, de Sauvage FJ, McMahon AP, Gilliland DG. Hedgehog signaling is dispensable for adult murine hematopoietic stem cell function and hematopoiesis. Cell Stem Cell. 2009 Jun 5;4(6):559-67.
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Naveiras O, Nardi V, Wenzel PL, Hauschka PV, Fahey F, Daley GQ. Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment. Nature. 2009 Jul 9;460(7252):259-63. Epub 2009 Jun 10.
Read Abstract.
Cancer
Smith A, Blois J, Yuan H, Aikawa E, Ellson C, Figueiredo JL, Weissleder R Kohler R, Yaffe MB, Cantley LC, Josephson L. The antiproliferative cytostatic effects of a self-activating viridin prodrug. Mol Cancer Ther. 2009 Jun;8(6):1666-75. Epub 2009 Jun 9.
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Xu D, Holko M, Sadler AJ, Scott B, Higashiyama S, Berkofsky-Fessler W, McConnell MJ, Pandolfi PP, Licht JD, Williams BR. Promyelocytic leukemia zinc finger protein regulates interferon-mediated innate immunity. Immunity. 2009 Jun 19;30(6):802-16. Epub 2009 Jun 11.
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Cardiovascular System
Takeda M, Briggs LE, Wakimoto H, Marks MH, Warren SA, Lu JT, Weinberg EO, Robertson KD, Chien KR, Kasahara H. Slow progressive conduction and contraction defects in loss of Nkx2-5 mice after cardiomyocyte terminal differentiation. Lab Invest. 2009 Jun 22. [Epub ahead of print]
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Zhou B, Ma Q, Kong SW, Hu Y, Campbell PH, McGowan FX, Ackerman KG, Wu B, Zhou B, Tevosian SG, Pu WT. Fog2 is critical for cardiac function and maintenance of coronary vasculature in the adult mouse heart. J Clin Invest. 2009 Jun;119(6):1462-76.
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Developmental Biology
Chen L, Yabuuchi A, Eminli S, Takeuchi A, Lu CW, Hochedlinger K, Daley GQ. Cross-regulation of the Nanog and Cdx2 promoters. Cell Res. 2009 Jun 30. [Epub ahead of print]
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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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Hilderbrand SA, Shao F, Salthouse C, Mahmood U, Weissleder R. Upconverting luminescent nanomaterials: application to in vivo bioimaging. Chem Commun (Camb). 2009 Jul 28;(28):4188-90. Epub 2009 Jun 12.
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Lee H, Yoon TJ, Weissleder R. Ultrasensitive Detection of Bacteria Using Core-Shell Nanoparticles and an NMR-Filter System. Angew Chem Int Ed Engl. 2009 Jun 24;48(31):5657-5660. [Epub ahead of print]
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McCarthy JR, Patel P, Botnaru I, Haghayeghi P, Weissleder R, Jaffer FA. Multimodal nanoagents for the detection of intravascular thrombi. Bioconjug Chem. 2009 Jun;20(6):1251-5.
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Vinegoni C, Razansky D, Figueiredo JL, Fexon L, Pivovarov M, Nahrendorf M, Ntziachristos V, Weissleder R. Born normalization for fluorescence optical projection tomography for whole heart imaging. J Vis Exp. 2009 Jun 2;(28). pii: 1389. doi: 10.3791/1389.
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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 Jun 12. [Epub ahead of print]
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Immunology
Guerau-de-Arellano M, Martinic M, Benoist C, Mathis D. Neonatal tolerance revisited: a perinatal window for Aire control of autoimmunity. J Exp Med. 2009 Jun 8;206(6):1245-52. Epub 2009 Jun 1.
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Kasorn A, Alcaide P, Jia Y, Subramanian KK, Sarraj B, Li Y, Loison F, Hattori H, Silberstein LE, Luscinskas WF, Luo HR. Focal adhesion kinase regulates pathogen-killing capability and life span of neutrophils via mediating both adhesion-dependent and -independent cellular signals. J Immunol. 2009 Jul 15;183(2):1032-43. Epub 2009 Jun 26.
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Sarraj B, Massberg S, Li Y, Kasorn A, Subramanian K, Loison F, Silberstein LE, von Andrian U, Luo HR. Myeloid-specific deletion of tumor suppressor PTEN augments neutrophil transendothelial migration during inflammation. J Immunol. 2009 Jun 1;182(11):7190-200.
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Molecular Biology
Faye C, Moreau C, Chautard E, Jetne R, Fukai N, Ruggiero F, Humphries MJ, Olsen BR, Ricard-Blum S. Molecular interplay between endostatin, integrins, and heparan sulfate. J Biol Chem. 2009 Jun 5. [Epub ahead of print]
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Ponnuswamy P, Ostermeier E, Schröttle A, Chen J, Huang PL, Ertl G, Nieswandt B, Kuhlencordt PJ. Oxidative stress and compartment of gene expression determine proatherosclerotic effects of inducible nitric oxide synthase. Am J Pathol. 2009 Jun;174(6):2400-10.
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Nervous System
Astradsson A, Jenkins BG, Choi JK, Hallett PJ, Levesque MA, McDowell JS, Brownell AL, Spealman RD, Isacson O. The blood-brain barrier is intact after levodopa-induced dyskinesias in parkinsonian primates-Evidence from in vivo neuroimaging studies. Neurobiol Dis. 2009 Jun 6. [Epub ahead of print]
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Renal System
Georgas K, Rumballe B, Valerius MT, Chiu HS, Thiagarajan RD, Lesieur E, Aronow BJ, Brunskill EW, Combes AN, Tang D, Taylor D, Grimmond SM, Potter SS, McMahon AP, Little MH. Analysis of early nephron patterning reveals a role for distal RV proliferation in fusion to the ureteric tip via a cap mesenchyme-derived connecting segment. Dev Biol. 2009 Jun 6. [Epub ahead of print]
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Nijboer WN, Schuurs TA, Damman J, van Goor H, Vaidya VS, van der Heide JJ, Leuvenink HG, Bonventre JV, Ploeg RJ. Kidney Injury Molecule-1 is an Early Noninvasive Indicator for Donor Brain Death-Induced Injury Prior to Kidney Transplantation. Am J Transplant. 2009 Jun 12. [Epub ahead of print]
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Zhang J, Goering PL, Espandiari P, Shaw M, Bonventre JV, Vaidya VS, Brown RP, Keenan J, Kilty CG, Sadrieh N, Hanig JP. Differences in Immunolocalization of Kim-1, RPA-1, and RPA-2 in Kidneys of Gentamicin-, Cisplatin-, and Valproic Acid-Treated Rats: Potential Role of iNOS and Nitrotyrosine. Toxicol Pathol. 2009 Jun 17. [Epub ahead of print]
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Skeletal System
Faye C, Chautard E, Olsen BR, Ricard-Blum S. The first draft of the endostatin interaction network. J Biol Chem. 2009 Jun 19. [Epub ahead of print]
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Skin
Huang SJ, Hijnen D, Murphy GF, Kupper TS, Calarese AW, Mollet IG, Schanbacher CF, Miller DM, Schmults CD, Clark RA. Imiquimod Enhances IFN-gamma Production and Effector Function of T Cells Infiltrating Human Squamous Cell Carcinomas of the Skin. J Invest Dermatol. 2009 Jun 11. [Epub ahead of print]
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Technology
Kuhn E, Addona T, Keshishian H, Burgess M, Mani DR, Lee RT, Sabatine MS, Gerszten RE, Carr SA. Developing multiplexed assays for troponin I and interleukin-33 in plasma by peptide immunoaffinity enrichment and targeted mass spectrometry. Clin Chem. 2009 Jun;55(6):1108-17. Epub 2009 Apr 16.
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Zou J, Maeder ML, Mali P, Pruett-Miller SM, Thibodeau-Beganny S, Chou BK, Chen G, Ye Z, Park IH, Daley GQ, Porteus MH, Joung JK, Cheng L. Gene targeting of a disease-related gene in human induced pluripotent stem and embryonic stem cells. Cell Stem Cell. 2009 Jul 2;5(1):97-110. Epub 2009 Jun 18.
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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. 2009 Jun;15(6):1321-9.
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