Research Newsletter - June 2009
Spotlight
Two groups of HSCI researchers from Children's Hospital Boston and Brigham and Women's Hospital - presenting multiple lines of evidence from zebrafish, mice, and mouse embryonic stem cells - have shown that a beating heart and blood flow are necessary for development of the blood system, which relies on mechanical stresses to cue its formation.
These studies, published in the journals Cell and Nature, together offer clues that may help in treating blood diseases such as leukemia, immune deficiency, and sickle cell anemia, and suggest new ways that scientists can make the types of blood cells a patient needs.
Hematopoietic stem cell development is dependent on blood flow
Abstract:
During vertebrate embryogenesis, hematopoietic stem cells (HSCs) arise in the aorta-gonads-mesonephros (AGM) region. We report here that blood flow is a conserved regulator of HSC formation. In zebrafish, chemical blood flow modulators regulated HSC development, and silent heart (sih) embryos, lacking a heartbeat and blood circulation, exhibited severely reduced HSCs. Flow-modifying compounds primarily affected HSC induction after the onset of heartbeat; however, nitric oxide (NO) donors regulated HSC number even when treatment occurred before the initiation of circulation, and rescued HSCs in sih mutants. Morpholino knockdown of nos1 (nnos/enos) blocked HSC development, and its requirement was shown to be cell autonomous. In the mouse, Nos3 (eNos) was expressed in HSCs in the AGM. Intrauterine Nos inhibition or embryonic Nos3 deficiency resulted in a reduction of hematopoietic clusters and transplantable murine HSCs. This work links blood flow to AGM hematopoiesis and identifies NO as a conserved downstream regulator of HSC development.
North TE, Goessling W, Peeters M, Li P, Ceol C, Lord AM, Weber GJ, Harris J, Cutting CC, Huang P, Dzierzak E, Zon LI. Hematopoietic stem cell development is dependent on blood flow. Cell. 2009 May 15;137(4):736-48. Read Paper.
Biomechanical forces promote embryonic haematopoiesis
Abstract:
Biomechanical forces are emerging as critical regulators of embryogenesis, particularly in the developing cardiovascular system. After initiation of the heartbeat in vertebrates, cells lining the ventral aspect of the dorsal aorta, the placental vessels, and the umbilical and vitelline arteries initiate expression of the transcription factor Runx1 (refs 3-5), a master regulator of haematopoiesis, and give rise to haematopoietic cells. It remains unknown whether the biomechanical forces imposed on the vascular wall at this developmental stage act as a determinant of haematopoietic potential. Here, using mouse embryonic stem cells differentiated in vitro, we show that fluid shear stress increases the expression of Runx1 in CD41(+)c-Kit(+) haematopoietic progenitor cells, concomitantly augmenting their haematopoietic colony-forming potential. Moreover, we find that shear stress increases haematopoietic colony-forming potential and expression of haematopoietic markers in the para-aortic splanchnopleura/aorta-gonads-mesonephros of mouse embryos and that abrogation of nitric oxide, a mediator of shear-stress-induced signalling, compromises haematopoietic potential in vitro and in vivo. Collectively, these data reveal a critical role for biomechanical forces in haematopoietic development.
Adamo L, Naveiras O, Wenzel PL, McKinney-Freeman S, Mack PJ, Gracia-Sancho J, Suchy-Dicey A, Yoshimoto M, Lensch MW, Yoder MC, García-Cardeña G, Daley GQ. Biomechanical forces promote embryonic haematopoiesis. Nature. 2009 May 13. [Epub ahead of print] Read Paper.
Review and Commentary
Boye E, Olsen BR. Signaling mechanisms in infantile hemangioma. Curr Opin Hematol. 2009 May;16(3):202-8.
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Cancelas JA, Williams DA. Rho GTPases in hematopoietic stem cell functions. Curr Opin Hematol. 2009 May 2. [Epub ahead of print]
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Huang PL. A comprehensive definition for metabolic syndrome. Dis Model Mech. 2009 May-Jun;2(5-6):231-7.
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Khademhosseini A, Vacanti JP, Langer R. Progress in tissue engineering. Sci Am. 2009 May;300(5):64-71.
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Nathan DG, Orkin SH. Musings on genome medicine: cancer genetics and the promise of effective treatment. Genome Med. 2009 May 6;1(5):49. [Epub ahead of print]
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Stadtfeld M, Hochedlinger K. Without a trace? PiggyBac-ing toward pluripotency. Nat Methods. 2009 May;6(5):329-30.
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Williams DA. Recombinant DNA advisory committee updates recommendations on gene transfer for x-linked severe combined immunodeficiency. Mol Ther. 2009 May;17(5):751-2.
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Blood
Adamo L, Naveiras O, Wenzel PL, McKinney-Freeman S, Mack PJ, Gracia-Sancho J, Suchy-Dicey A, Yoshimoto M, Lensch MW, Yoder MC, García-Cardeña G, Daley GQ. Biomechanical forces promote embryonic haematopoiesis. Nature. 2009 May 13. [Epub ahead of print]
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McKinney-Freeman SL, Naveiras O, Yates F, Loewer S, Philitas M, Curran M, Park PJ, Daley GQ. Surface antigen phenotypes of hematopoietic stem cells from embryos and murine embryonic stem cells. Blood. 2009 May 6. [Epub ahead of print]
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North TE, Goessling W, Peeters M, Li P, Ceol C, Lord AM, Weber GJ, Harris J, Cutting CC, Huang P, Dzierzak E, Zon LI. Hematopoietic stem cell development is dependent on blood flow. Cell. 2009 May 15;137(4):736-48.
Read Abstract.
Singh TR, Bakker ST, Agarwal S, Jansen M, Grassman E, Godthelp BC, Ali AM, Du CH, Rooimans MA, Fan Q, Wahengbam K, Steltenpool J, Andreassen PR, Williams DA, Joenje H, de Winter JP, Meetei AR. Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M. Blood. 2009 May 7. [Epub ahead of print]
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Stachura DL, Reyes JR, Bartunek P, Paw BH, Zon LI, Traver D. Zebrafish kidney stromal cell lines support multilineage hematopoiesis. Blood. 2009 May 11. [Epub ahead of print]
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Cancer
Abdel-Wahab O, Mullally A, Hedvat C, Garcia-Manero G, Patel J, Wadleigh M, Malinge S, Yao J, Kilpivaara O, Bhat R, Huberman K, Thomas S, Dolgalev I, Heguy A, Paietta E, Le Beau MM, Beran M, Tallman MS, Ebert BL, Kantarjian HM, Stone RM, Gilliland DG, Crispino JD, Levine RL. Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies. Blood. 2009 May 6. [Epub ahead of print]
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Baek KH, Zaslavsky A, Lynch RC, Britt C, Okada Y, Siarey RJ, Lensch MW, Park IH, Yoon SS, Minami T, Korenberg JR, Folkman J, Daley GQ, Aird WC, Galdzicki Z, Ryeom S. Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1. Nature. 2009 May 20. [Epub ahead of print]
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Gutierrez A, Sanda T, Grebliunaite R, Carracedo A, Salmena L, Ahn Y, Dahlberg S, Neuberg D, Moreau LA, Winter SS, Larson R, Zhang J, Protopopov A, Chin L, Pandolfi PP, Silverman LB, Hunger SP, Sallan SE, Look AT. High frequency of PTEN, PI3K and AKT abnormalities in T cell acute lymphoblastic leukemia. Blood. 2009 May 20. [Epub ahead of print]
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Jeter CR, Badeaux M, Choy G, Chandra D, Patrawala L, Liu C, Calhoun-Davis T, Zaehres H, Daley GQ, Tang DG. Functional evidence that the self-renewal gene NANOG regulates human tumor development. Stem Cells. 2009 May;27(5):993-1005.
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Le Y, Xu L, Lu J, Fang J, Nardi V, Chai L, Silberstein LE. FAK silencing inhibits leukemogenesis in BCR/ABL-transformed hematopoietic cells. Am J Hematol. 2009 May;84(5):273-8.
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Salazar M, Carracedo A, Salanueva IJ, Hernández-Tiedra S, Lorente M, Egia A, Vázquez P, Blázquez C, Torres S, García S, Nowak J, Fimia GM, Piacentini M, Cecconi F, Pandolfi PP, González-Feria L, Iovanna JL, Guzmán M, Boya P, Velasco G. Cannabinoid action induces autophagymediated cell death through stimulation of ER stress in human glioma cells. J Clin Invest. 2009 May;119(5):1359-72.
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Viswanathan SR, Powers JT, Einhorn W, Hoshida Y, Ng TL, Toffanin S, O'Sullivan M, Lu J, Phillips LA, Lockhart VL, Shah SP, Tanwar PS, Mermel CH, Beroukhim R, Azam M, Teixeira J, Meyerson M, Hughes TP, Llovet JM, Radich J, Mullighan CG, Golub TR, Sorensen PH, Daley GQ. Lin28 promotes transformation and is associated with advanced human malignancies. Nat Genet. 2009 May 31. [Epub ahead of print]
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Cardiovascular System
Park HJ, Zhang Y, Du C, Welzig CM, Madias C, Aronovitz MJ, Georgescu SP, Naggar I, Wang B, Kim YB, Blaustein RO, Karas RH, Liao R, Mathews CE, Galper JB. Role of SREBP-1 in the Development of Parasympathetic Dysfunction in the Hearts of Type 1 Diabetic Akita Mice. Circ Res. 2009 May 7. [Epub ahead of print]
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Yan J, Young ME, Cui L, Lopaschuk GD, Liao R, Tian R. Increased glucose uptake and oxidation in mouse hearts prevent high Fatty Acid oxidation but cause cardiac dysfunction in diet-induced obesity. Circulation. 2009 Jun 2;119(21):2818-28. Epub 2009 May 18.
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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 May 1. pii: 38723. doi: 10.1172/JCI38723. [Epub ahead of print]
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Developmental Biology
Cherry TJ, Trimarchi JM, Stadler MB, Cepko CL. Development and diversification of retinal amacrine interneurons at single cell resolution. Proc Natl Acad Sci USA. 2009 May 26. [Epub ahead of print]
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Dyer MA, Martins R, da Silva Filho M, Muniz JA, Silveira LC, Cepko CL, Finlay BL. Developmental sources of conservation and variation in the evolution of the primate eye. Proc Natl Acad Sci fUSA. 2009 May 18. [Epub ahead of print]
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Han DW, Do JT, Araúzo-Bravo MJ, Lee SH, Meissner A, Lee HT, Jaenisch R, Schöler HR. Epigenetic hierarchy governing Nestin expression. Stem Cells. 2009 May;27(5):1088-97.
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Jadhav AP, Roesch K, Cepko CL. Development and neurogenic potential of Müller glial cells in the vertebrate retina. Prog Retin Eye Res. 2009 May 22. [Epub ahead of print]
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Lu J, Jeong H, Kong N, Yang Y, Carroll J, Luo HR, Silberstein LE, Yupoma, Chai L. Stem cell factor SALL4 represses the transcriptions of PTEN and SALL1 through an epigenetic repressor complex. PLoS ONE. 2009;4(5):e5577. Epub 2009 May 18.
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Trimarchi JM, Cho SH, Cepko CL. Identification of genes expressed preferentially in the developing peripheral margin of the optic cup. Dev Dyn. 2009 May 14. [Epub ahead of print]
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Imaging
Koh I, Hong R, Weissleder R, Josephson L. Nanoparticle-target interactions parallel antibody-protein interactions. Anal Chem. 2009 May 1;81(9):3618-22.
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Leimgruber A, Berger C, Cortez-Retamozo V, Etzrodt M, Newton AP, Waterman P, Figueiredo JL, Kohler RH, Elpek N, Mempel TR, Swirski FK, Nahrendorf M, Weissleder R, Pittet MJ. Behavior of endogenous tumor-associated macrophages assessed in vivo using a functionalized nanoparticle. Neoplasia. 2009 May;11(5):459-68, 2 p following 468.
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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 May 20. [Epub ahead of print]
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Wildgruber M, Lee H, Chudnovskiy A, Yoon TJ, Etzrodt M, Pittet MJ, Nahrendorf M, Croce K, Libby P, Weissleder R, Swirski FK. Monocyte subset dynamics in human atherosclerosis can be profiled with magnetic nano-sensors. PLoS ONE. 2009 May 22;4(5):e5663.
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Muscular System
Kumar D, Shadrach JL, Wagers AJ, Lassar AB. Id3 Is a Direct Transcriptional Target of Pax7 in Quiescent Satellite Cells. Mol Biol Cell. 2009 May 20. [Epub ahead of print]
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Lee Sohn R, Huang P, Kawahara G, Mitchell M, Guyon J, Kalluri R, Kunkel LM, Gussoni E. A role for nephrin, a renal protein, in vertebrate skeletal muscle cell fusion. Proc Natl Acad Sci USA. 2009 May 22. [Epub ahead of print]
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Mizuno Y, Guyon JR, Okamoto K, Kunkel LM. Expression of synemin in the mouse spinal cord. Muscle Nerve. 2009 May;39(5):634-41.
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Pulmonary System
Jones R, Capen DE, Jacobson M, Cohen KS, Scadden DT, Duda DG. VEGFR2PDGFRbeta circulating precursor cells participate in capillary restoration after hyperoxia acute lung injury (HALI). J Cell Mol Med. 2009 May 6. [Epub ahead of print]
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Skin
Mitchell K, Szekeres C, Milano V, Svenson KB, Nilsen-Hamilton M, Kreidberg JA, Dipersio CM. {alpha}3{beta}1 integrin in epidermis promotes wound angiogenesis and keratinocyte-to-endothelial-cell crosstalk through the induction of MRP3. J Cell Sci. 2009 Jun 1;122(Pt 11):1778-87. Epub 2009 May 12.
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Technology
Smith ZD, Gu H, Bock C, Gnirke A, Meissner A. High-throughput bisulfite sequencing in mammalian genomes. Methods. 2009 May 12. [Epub ahead of print]
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Tsuchiya M, Bojarczuk NA, Guha S, Ramanathan S. Microstructural effects on electrical conductivity relaxation in nanoscale ceria thin films. J Chem Phys. 2009 May 7;130(17):174711.
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