Research Newsletter - August 2009
Spotlight
In an article paper published in Nature, HSCI Executive Committee Member Kenneth Chien, MD, PhD, Principal Faculty member Paul Huang, MD, PhD, and colleagues show that that purified ISL1(+) primordial progenitors are capable of self-renewal and expansion before differentiation into the three major cell types in the heart.
Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages
Abstract:
The generation and expansion of diverse cardiovascular cell lineages is a critical step during human cardiogenesis, with major implications for congenital heart disease. Unravelling the mechanisms for the diversification of human heart cell lineages has been hampered by the lack of genetic tools to purify early cardiac progenitors and define their developmental potential. Recent studies in the mouse embryo have identified a multipotent cardiac progenitor that contributes to all of the major cell types in the murine heart. In contrast to murine development, human cardiogenesis has a much longer onset of heart cell lineage diversification and expansion, suggesting divergent pathways. Here we identify a diverse set of human fetal ISL1(+) cardiovascular progenitors that give rise to the cardiomyocyte, smooth muscle and endothelial cell lineages. Using two independent transgenic and gene-targeting approaches in human embryonic stem cell lines, we show that purified ISL1(+) primordial progenitors are capable of self-renewal and expansion before differentiation into the three major cell types in the heart. These results lay the foundation for the generation of human model systems for cardiovascular disease and novel approaches for human regenerative cardiovascular medicine.
Bu L, Jiang X, Martin-Puig S, Caron L, Zhu S, Shao Y, Roberts DJ, Huang PL, Domian IJ, Chien KR. Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages. Nature. 2009 Jul 2;460(7251):113-7. Read Paper.
Review and Commentary
Cancelas JA, Williams DA. Rho GTPases in hematopoietic stem cell functions. Curr Opin Hematol. 2009 Jul;16(4):249-54.
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Feuerer M, Hill JA, Mathis D, Benoist C. Foxp3+ regulatory T cells: differentiation, specification, subphenotypes. Nat Immunol. 2009 Jul;10(7):689-95.
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Geijsen N, Hochedlinger K. gPS navigates germ cells to pluripotency. Cell Stem Cell. 2009 Jul 2;5(1):3-4.
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Goessling W. Deciphering Hepatocellular Carcinoma: From Bench to Bedside and Back. Gastroenterology. 2009 Jul 27. [Epub ahead of print]
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Wu CJ, Ritz J. Revealing tumor immunity after hematopoietic stem cell transplantation. Clin Cancer Res. 2009 Jul 15;15(14):4515-7. Epub 2009 Jul 7.
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Aging
Oliveira RP, Porter Abate J, Dilks K, Landis J, Ashraf J, Murphy CT, Blackwell TK. Condition-adapted stress and longevity gene regulation by Caenorhabditis elegans SKN-1/Nrf. Aging Cell. 2009 Jul 3. [Epub ahead of print]
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Blood
Huang Z, Dore LC, Li Z, Orkin SH, Feng G, Lin S, Crispino JD. GATA-2 reinforces megakaryocyte development in the absence of GATA-1. Mol Cell Biol. 2009 Jul 20. [Epub ahead of print]
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Schindler JW, Van Buren D, Foudi A, Krejci O, Qin J, Orkin SH, Hock H. TEL-AML1 corrupts hematopoietic stem cells to persist in the bone marrow and initiate leukemia. Cell Stem Cell. 2009 Jul 2;5(1):43-53.
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Cancer
Baba Y, Nosho K, Shima K, Freed E, Irahara N, Philips J, Meyerhardt JA, Hornick JL, Shivdasani RA, Fuchs CS, Ogino S. Relationship of CDX2 loss with molecular features and prognosis in colorectal cancer. Clin Cancer Res. 2009 Jul 15;15(14):4665-73. Epub 2009 Jul 7.
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Lee H, Yoon TJ, Figueiredo JL, Swirski FK, Weissleder R. Rapid detection and profiling of cancer cells in fine-needle aspirates. Proc Natl Acad Sci USA. 2009 Jul 20. [Epub ahead of print]
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Souglakos J, Philips J, Wang R, Marwah S, Silver M, Tzardi M, Silver J, Ogino S, Hooshmand S, Kwak E, Freed E, Meyerhardt JA, Saridaki Z, Georgoulias V, Finkelstein D, Fuchs CS, Kulke MH, Shivdasani RA. Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer. Br J Cancer. 2009 Aug 4;101(3):465-72. Epub 2009 Jul 14.
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Yoon SS, Stangenberg L, Lee YJ, Rothrock C, Dreyfuss JM, Baek KH, Waterman PR, Nielsen GP, Weissleder R, Mahmood U, Park PJ, Jacks T, Dodd RD, Fisher CJ, Ryeom S, Kirsch DG. Efficacy of sunitinib and radiotherapy in genetically engineered mouse model of soft-tissue sarcoma. Int J Radiat Oncol Biol Phys. 2009 Jul 15;74(4):1207-16.
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Cardiovascular System
Bu L, Jiang X, Martin-Puig S, Caron L, Zhu S, Shao Y, Roberts DJ, Huang PL, Domian IJ, Chien KR. Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages. Nature. 2009 Jul 2;460(7251):113-7.
Read Abstract.
Developmental Biology
Viswanathan SR, Mermel CH, Lu J, Lu CW, Golub TR, Daley GQ. microRNA expression during trophectoderm specification. PLoS One. 2009 Jul 3;4(7):e6143.
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West JA, Viswanathan SR, Yabuuchi A, Cunniff K, Takeuchi A, Park IH, Sero JE, Zhu H, Perez-Atayde A, Frazier AL, Surani MA, Daley GQ. A role for Lin28 in primordial germ-cell development and germ-cell malignancy. Nature. 2009 Jul 5. [Epub ahead of print]
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Diabetes
Genetics and Genomics
Ali AM, Kirby M, Jansen M, Lach FP, Schulte J, Singh TR, Batish SD, Auerbach AD, Williams DA, Meetei AR. Identification and characterization of mutations in FANCL gene: a second case of Fanconi anemia belonging to FA-L complementation group. Hum Mutat. 2009 Jul;30(7):E761-70.
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Imaging
Bhaumik J, Weissleder R, McCarthy JR. Synthesis and Photophysical Properties of Sulfonamidophenyl Porphyrins as Models for Activatable Photosensitizers. J Org Chem. 2009 Jul 17. [Epub ahead of print]
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Nahrendorf M, Waterman P, Thurber G, Groves K, Rajopadhye M, Panizzi P, Marinelli B, Aikawa E, Pittet MJ, Swirski FK, Weissleder R. Hybrid In Vivo FMT-CT Imaging of Protease Activity in Atherosclerosis With Customized Nanosensors. Arterioscler Thromb Vasc Biol. 2009 Jul 16. [Epub ahead of print]
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Ross RW, Zietman AL, Xie W, Coen JJ, Dahl DM, Shipley WU, Kaufman DS, Islam T, Guimaraes AR, Weissleder R, Harisinghani M. Lymphotropic nanoparticle-enhanced magnetic resonance imaging (LNMRI) identifies occult lymph node metastases in prostate cancer patients prior to salvage radiation therapy. Clin Imaging. 2009 Jul-Aug;33(4):301-5.
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Immunology
Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A, Lee J, Goldfine AB, Benoist C, Shoelson S, Mathis D. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med. 2009 Jul 26. [Epub ahead of print]
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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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Kreslavsky T, Savage AK, Hobbs R, Gounari F, Bronson R, Pereira P, Pandolfi PP, Bendelac A, von Boehmer H. TCR-inducible PLZF transcription factor required for innate phenotype of a subset of {gamma}{delta} T cells with restricted TCR diversity. Proc Natl Acad Sci USA. 2009 Jul 15. [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 Jul 30;60(8):2314-2324. [Epub ahead of print]
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Swirski FK, Nahrendorf M, Etzrodt M, Wildgruber M, Cortez-Retamozo V, Panizzi P, Figueiredo JL, Kohler RH, Chudnovskiy A, Waterman P, Aikawa E, Mempel TR, Libby P, Weissleder R, Pittet MJ. Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science. 2009 Jul 31;325(5940):612-6.
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Molecular Biology
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 Jul 2. [Epub ahead of print]
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Lamour NF, Subramanian P, Wijesinghe DS, Stahelin RV, Bonventre JV, Chalfant CE. Ceramide-1-phosphate is required for the translocation of group IVA cytosolic phospholipase A2 and prostaglandin synthesis. J Biol Chem. 2009 Jul 23. [Epub ahead of print]
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Pain
Binshtok AM, Gerner P, Oh SB, Puopolo M, Suzuki S, Roberson DP, Herbert T, Wang CF, Kim D, Chung G, Mitani AA, Wang GK, Bean BP, Woolf CJ. Coapplication of lidocaine and the permanently charged sodium channel blocker QX-314 produces a long-lasting nociceptive blockade in rodents. Anesthesiology. 2009 Jul;111(1):127-37.
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Renal System
Liangos O, Tighiouart H, Perianayagam MC, Kolyada A, Han WK, Wald R, Bonventre JV, Jaber BL. Comparative analysis of urinary biomarkers for early detection of acute kidney injury following cardiopulmonary bypass. Biomarkers. 2009 Jul 2. [Epub ahead of print]
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Mugford JW, Yu J, Kobayashi A, McMahon AP. High-resolution gene expression analysis of the developing mouse kidney defines novel cellular compartments within the nephron progenitor population. Dev Biol. 2009 Jul 8. [Epub ahead of print]
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Technology
Zhang K, Li JB, Gao Y, Egli D, Xie B, Deng J, Li Z, Lee JH, Aach J, Leproust EM, Eggan K, Church GM. Digital RNA allelotyping reveals tissue-specific and allele-specific gene expression in human. Nat Methods. 2009 Aug;6(8):613-8. Epub 2009 Jul 20.
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