{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T01:57:51Z","timestamp":1785031071509,"version":"3.55.0"},"reference-count":68,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,2,17]],"date-time":"2017-02-17T00:00:00Z","timestamp":1487289600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,2,17]],"date-time":"2017-02-17T00:00:00Z","timestamp":1487289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sig Transduct Target Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In mammals, the livers regenerate after chemical injury or resection of hepatic lobe by hepatectomy. How liver regeneration is initiated after mass loss remains to be defined. Here we report that following liver injury, activated platelets deploy SDF-1 and VEGF-A to stimulate CXCR7<jats:sup>+<\/jats:sup> liver sinusoidal endothelial cell (LSEC) and VEGFR1<jats:sup>+<\/jats:sup> myeloid cell, orchestrating hepatic regeneration. After carbon tetrachloride injection or hepatectomy, platelets and CD11b<jats:sup>+<\/jats:sup>VEGFR1<jats:sup>+<\/jats:sup> myeloid cells were recruited to LSECs, and liver regeneration in both models was impaired in thrombopoietin-deficient (<jats:italic>Thpo<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>) mice repressing production of circulating platelets. This impeded regeneration phenotype was recapitulated in mice with either conditional ablation of <jats:italic>Cxcr7<\/jats:italic> in LSEC (<jats:italic>Cxcr7<\/jats:italic><jats:sup>i\u0394\/i\u0394<\/jats:sup>) or <jats:italic>Vegfr1<\/jats:italic> in myeloid cell (<jats:italic>Vegfr1<\/jats:italic><jats:sup>lysM\/lysM<\/jats:sup>). Both <jats:italic>Vegfr1<\/jats:italic><jats:sup>lysM\/lysM<\/jats:sup> and <jats:italic>Cxcr7<\/jats:italic><jats:sup>i\u0394\/i\u0394<\/jats:sup> mice exhibited suppressed expression of hepatocyte growth factor and Wnt2, two crucial trophogenic angiocrine factors instigating hepatocyte propagation. Of note, administration of recombinant thrombopoietin restored the prohibited liver regeneration in the tested genetic models. As such, our data suggest that platelets and myeloid cells jointly activate the vascular niche to produce pro-regenerative endothelial paracrine\/angiocrine factors. Modulating this \u2018hematopoietic\u2013vascular niche\u2019 might help to develop regenerative therapy strategy for hepatic disorders.<\/jats:p>","DOI":"10.1038\/sigtrans.2016.44","type":"journal-article","created":{"date-parts":[[2017,2,17]],"date-time":"2017-02-17T09:57:04Z","timestamp":1487325424000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Platelets prime hematopoietic\u2013vascular niche to drive angiocrine-mediated liver regeneration"],"prefix":"10.1038","volume":"2","author":[{"given":"Koji","family":"Shido","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deebly","family":"Chavez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongwei","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane L","family":"Ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahin","family":"Rafii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bi-Sen","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,2,17]]},"reference":[{"key":"BFsigtrans201644_CR1","doi-asserted-by":"publisher","first-page":"S45","DOI":"10.1002\/hep.20969","volume":"43","author":"N Fausto","year":"2006","unstructured":"Fausto N, Campbell JS, Riehle KJ . Liver regeneration. Hepatology 2006; 43: S45\u2013S53.","journal-title":"Hepatology"},{"key":"BFsigtrans201644_CR2","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1126\/science.276.5309.60","volume":"276","author":"GK Michalopoulos","year":"1997","unstructured":"Michalopoulos GK, DeFrances MC . Liver regeneration. Science 1997; 276: 60\u201366.","journal-title":"Science"},{"key":"BFsigtrans201644_CR3","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1126\/science.1244880","volume":"343","author":"J Hu","year":"2014","unstructured":"Hu J, Srivastava K, Wieland M, Runge A, Mogler C, Besemfelder E et al. Endothelial cell-derived angiopoietin-2 controls liver regeneration as a spatiotemporal rheostat. Science 2014; 343: 416\u2013419.","journal-title":"Science"},{"key":"BFsigtrans201644_CR4","doi-asserted-by":"publisher","first-page":"1490","DOI":"10.1126\/science.1161431","volume":"322","author":"KS Zaret","year":"2008","unstructured":"Zaret KS, Grompe M . Generation and regeneration of cells of the liver and pancreas. Science 2008; 322: 1490\u20131494.","journal-title":"Science"},{"key":"BFsigtrans201644_CR5","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1053\/j.gastro.2008.03.003","volume":"134","author":"SL Friedman","year":"2008","unstructured":"Friedman SL . Mechanisms of hepatic fibrogenesis. Gastroenterology 2008; 134: 1655\u20131669.","journal-title":"Gastroenterology"},{"key":"BFsigtrans201644_CR6","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1038\/nm.2719","volume":"18","author":"AM Diehl","year":"2012","unstructured":"Diehl AM . Neighborhood watch orchestrates liver regeneration. Nat Med 2012; 18: 497\u2013499.","journal-title":"Nat Med"},{"key":"BFsigtrans201644_CR7","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1172\/JCI30542","volume":"117","author":"JP Iredale","year":"2007","unstructured":"Iredale JP . Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ. J Clin Invest 2007; 117: 539\u2013548.","journal-title":"J Clin Invest"},{"key":"BFsigtrans201644_CR8","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1172\/JCI24282","volume":"115","author":"R Bataller","year":"2005","unstructured":"Bataller R, Brenner DA . Liver fibrosis. J Clin Invest 2005; 115: 209\u2013218.","journal-title":"J Clin Invest"},{"key":"BFsigtrans201644_CR9","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1172\/JCI200522675","volume":"115","author":"JS Duffield","year":"2005","unstructured":"Duffield JS, Forbes SJ, Constandinou CM, Clay S, Partolina M, Vuthoori S et al. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J Clin Invest 2005; 115: 56\u201365.","journal-title":"J Clin Invest"},{"key":"BFsigtrans201644_CR10","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1053\/gast.2003.50012","volume":"124","author":"C Yang","year":"2003","unstructured":"Yang C, Zeisberg M, Mosterman B, Sudhakar A, Yerramalla U, Holthaus K et al. Liver fibrosis: insights into migration of hepatic stellate cells in response to extracellular matrix and growth factors. Gastroenterology 2003; 124: 147\u2013159.","journal-title":"Gastroenterology"},{"key":"BFsigtrans201644_CR11","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1038\/nature09414","volume":"467","author":"AW Duncan","year":"2010","unstructured":"Duncan AW, Taylor MH, Hickey RD, Hanlon Newell AE, Lenzi ML, Olson SB et al. The ploidy conveyor of mature hepatocytes as a source of genetic variation. Nature 2010; 467: 707\u2013710.","journal-title":"Nature"},{"key":"BFsigtrans201644_CR12","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1053\/j.gastro.2011.11.030","volume":"142","author":"DH Woo","year":"2012","unstructured":"Woo DH, Kim SK, Lim HJ, Heo J, Park HS, Kang GY et al. Direct and indirect contribution of human embryonic stem cell-derived hepatocyte-like cells to liver repair in mice. Gastroenterology 2012; 142: 602\u2013611.","journal-title":"Gastroenterology"},{"key":"BFsigtrans201644_CR13","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1002\/hep.24815","volume":"55","author":"L Liu","year":"2012","unstructured":"Liu L, Yannam GR, Nishikawa T, Yamamoto T, Basma H, Ito R et al. The microenvironment in hepatocyte regeneration and function in rats with advanced cirrhosis. Hepatology 2012; 55: 1529\u20131539.","journal-title":"Hepatology"},{"key":"BFsigtrans201644_CR14","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1016\/j.cell.2009.01.015","volume":"136","author":"W Goessling","year":"2009","unstructured":"Goessling W, North TE, Loewer S, Lord AM, Lee S, Stoick-Cooper CL et al. Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell 2009; 136: 1136\u20131147.","journal-title":"Cell"},{"key":"BFsigtrans201644_CR15","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1038\/nature09493","volume":"468","author":"BS Ding","year":"2010","unstructured":"Ding BS, Nolan DJ, Butler JM, James D, Babazadeh AO, Rosenwaks Z et al. Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration. Nature 2010; 468: 310\u2013315.","journal-title":"Nature"},{"key":"BFsigtrans201644_CR16","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1126\/science.1079562","volume":"299","author":"J LeCouter","year":"2003","unstructured":"LeCouter J, Moritz DR, Li B, Phillips GL, Liang XH, Gerber HP et al. Angiogenesis-independent endothelial protection of liver: role of VEGFR-1. Science 2003; 299: 890\u2013893.","journal-title":"Science"},{"key":"BFsigtrans201644_CR17","doi-asserted-by":"publisher","first-page":"3980","DOI":"10.1172\/JCI35092","volume":"118","author":"AC Straub","year":"2008","unstructured":"Straub AC, Clark KA, Ross MA, Chandra AG, Li S, Gao X et al. Arsenic-stimulated liver sinusoidal capillarization in mice requires NADPH oxidase-generated superoxide. J Clin Invest 2008; 118: 3980\u20133989.","journal-title":"J Clin Invest"},{"key":"BFsigtrans201644_CR18","doi-asserted-by":"publisher","first-page":"1567","DOI":"10.1172\/JCI58789","volume":"122","author":"L Wang","year":"2012","unstructured":"Wang L, Wang X, Xie G, Wang L, Hill CK, Deleve LD . Liver sinusoidal endothelial cell progenitor cells promote liver regeneration in rats. J Clin Invest 2012; 122: 1567\u20131573.","journal-title":"J Clin Invest"},{"key":"BFsigtrans201644_CR19","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1016\/j.jhep.2007.02.006","volume":"46","author":"Y Iwakiri","year":"2007","unstructured":"Iwakiri Y, Groszmann RJ . Vascular endothelial dysfunction in cirrhosis. J Hepatol 2007; 46: 927\u2013934.","journal-title":"J Hepatol"},{"key":"BFsigtrans201644_CR20","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1053\/j.gastro.2007.06.021","volume":"133","author":"J Gracia-Sancho","year":"2007","unstructured":"Gracia-Sancho J, Lavina B, Rodriguez-Vilarrupla A, Brandes RP, Fernandez M, Bosch J et al. Evidence against a role for NADPH oxidase modulating hepatic vascular tone in cirrhosis. Gastroenterology 2007; 133: 959\u2013966.","journal-title":"Gastroenterology"},{"key":"BFsigtrans201644_CR21","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1002\/hep.23628","volume":"52","author":"RC Huebert","year":"2010","unstructured":"Huebert RC, Vasdev MM, Shergill U, Das A, Huang BQ, Charlton MR et al. Aquaporin-1 facilitates angiogenic invasion in the pathological neovasculature that accompanies cirrhosis. Hepatology 2010; 52: 238\u2013248.","journal-title":"Hepatology"},{"key":"BFsigtrans201644_CR22","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1002\/hep.21317","volume":"44","author":"U Apte","year":"2006","unstructured":"Apte U, Zeng G, Muller P, Tan X, Micsenyi A, Cieply B et al. Activation of Wnt\/beta-catenin pathway during hepatocyte growth factor-induced hepatomegaly in mice. Hepatology 2006; 44: 992\u20131002.","journal-title":"Hepatology"},{"key":"BFsigtrans201644_CR23","first-page":"e87058","volume":"1","author":"BS Ding","year":"2016","unstructured":"Ding BS, Liu CH, Sun Y, Chen Y, Swendeman SL, Jung B et al. HDL activation of endothelial sphingosine-1-phosphate receptor-1 (S1P1) promotes regeneration and suppresses fibrosis in the liver. JCI Insight 2016; 1: e87058.","journal-title":"JCI Insight"},{"key":"BFsigtrans201644_CR24","doi-asserted-by":"publisher","first-page":"4850","DOI":"10.1172\/JCI59261","volume":"121","author":"Y Malato","year":"2011","unstructured":"Malato Y, Naqvi S, Schurmann N, Ng R, Wang B, Zape J et al. Fate tracing of mature hepatocytes in mouse liver homeostasis and regeneration. J Clin Invest 2011; 121: 4850\u20134860.","journal-title":"J Clin Invest"},{"key":"BFsigtrans201644_CR25","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/ni.1855","volume":"11","author":"WY Lee","year":"2010","unstructured":"Lee WY, Moriarty TJ, Wong CH, Zhou H, Strieter RM, van Rooijen N et al. An intravascular immune response to Borrelia burgdorferi involves Kupffer cells and iNKT cells. Nat Immunol 2010; 11: 295\u2013302.","journal-title":"Nat Immunol"},{"key":"BFsigtrans201644_CR26","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1126\/science.1123842","volume":"312","author":"M Lesurtel","year":"2006","unstructured":"Lesurtel M, Graf R, Aleil B, Walther DJ, Tian Y, Jochum W et al. Platelet-derived serotonin mediates liver regeneration. Science 2006; 312: 104\u2013107.","journal-title":"Science"},{"key":"BFsigtrans201644_CR27","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1038\/nm.2667","volume":"18","author":"L Boulter","year":"2012","unstructured":"Boulter L, Govaere O, Bird TG, Radulescu S, Ramachandran P, Pellicoro A et al. Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease. Nat Med 2012; 18: 572\u2013579.","journal-title":"Nat Med"},{"key":"BFsigtrans201644_CR28","doi-asserted-by":"publisher","first-page":"2030","DOI":"10.1002\/hep.23591","volume":"51","author":"AI Aspinall","year":"2010","unstructured":"Aspinall AI, Curbishley SM, Lalor PF, Weston CJ, Liaskou E, Adams RM et al. CX(3)CR1 and vascular adhesion protein-1-dependent recruitment of CD16(+) monocytes across human liver sinusoidal endothelium. Hepatology 2010; 51: 2030\u20132039.","journal-title":"Hepatology"},{"key":"BFsigtrans201644_CR29","doi-asserted-by":"publisher","first-page":"2487","DOI":"10.1053\/j.gastro.2010.02.054","volume":"138","author":"T Kodama","year":"2010","unstructured":"Kodama T, Takehara T, Hikita H, Shimizu S, Li W, Miyagi T et al. Thrombocytopenia exacerbates cholestasis-induced liver fibrosis in mice. Gastroenterology 2010; 138: 2487\u20132498, 2498. e1\u20137.","journal-title":"Gastroenterology"},{"key":"BFsigtrans201644_CR30","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1016\/j.cub.2008.08.065","volume":"18","author":"TF Sakaguchi","year":"2008","unstructured":"Sakaguchi TF, Sadler KC, Crosnier C, Stainier DY . Endothelial signals modulate hepatocyte apicobasal polarization in zebrafish. Curr Biol 2008; 18: 1565\u20131571.","journal-title":"Curr Biol"},{"key":"BFsigtrans201644_CR31","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1126\/science.1063889","volume":"294","author":"K Matsumoto","year":"2001","unstructured":"Matsumoto K, Yoshitomi H, Rossant J, Zaret KS . Liver organogenesis promoted by endothelial cells prior to vascular function. Science 2001; 294: 559\u2013563.","journal-title":"Science"},{"key":"BFsigtrans201644_CR32","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.devcel.2007.01.013","volume":"12","author":"K Red-Horse","year":"2007","unstructured":"Red-Horse K, Crawford Y, Shojaei F, Ferrara N . Endothelium-microenvironment interactions in the developing embryo and in the adult. Dev Cell 2007; 12: 181\u2013194.","journal-title":"Dev Cell"},{"key":"BFsigtrans201644_CR33","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/ncb3096","volume":"17","author":"S Rafii","year":"2015","unstructured":"Rafii S, Cao Z, Lis R, Siempos II, Chavez D, Shido K et al. Platelet-derived SDF-1 primes the pulmonary capillary vascular niche to drive lung alveolar regeneration. Nat Cell Biol 2015; 17: 123\u2013136.","journal-title":"Nat Cell Biol"},{"key":"BFsigtrans201644_CR34","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/j.cell.2011.10.003","volume":"147","author":"BS Ding","year":"2011","unstructured":"Ding BS, Nolan DJ, Guo P, Babazadeh AO, Cao Z, Rosenwaks Z et al. Endothelial-derived angiocrine signals induce and sustain regenerative lung alveolarization. Cell 2011; 147: 539\u2013553.","journal-title":"Cell"},{"key":"BFsigtrans201644_CR35","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/nature12681","volume":"505","author":"BS Ding","year":"2014","unstructured":"Ding BS, Cao Z, Lis R, Nolan DJ, Guo P, Simons M et al. Divergent angiocrine signals from vascular niche balance liver regeneration and fibrosis. Nature 2014; 505: 97\u2013102.","journal-title":"Nature"},{"key":"BFsigtrans201644_CR36","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1038\/nature17040","volume":"529","author":"S Rafii","year":"2016","unstructured":"Rafii S, Butler JM, Ding BS . Angiocrine functions of organ-specific endothelial cells. Nature 2016; 529: 316\u2013325.","journal-title":"Nature"},{"key":"BFsigtrans201644_CR37","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1016\/j.ccr.2014.02.005","volume":"25","author":"Z Cao","year":"2014","unstructured":"Cao Z, Ding BS, Guo P, Lee SB, Butler JM, Casey SC et al. Angiocrine factors deployed by tumor vascular niche induce B cell lymphoma invasiveness and chemoresistance. Cancer Cell 2014; 25: 350\u2013365.","journal-title":"Cancer Cell"},{"key":"BFsigtrans201644_CR38","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.ccell.2016.11.010","volume":"31","author":"Z Cao","year":"2017","unstructured":"Cao Z, Scandura JM, Inghirami GG, Shido K, Ding BS, Rafii S . Molecular checkpoint decisions made by subverted vascular niche transform indolent tumor cells into chemoresistant cancer stem cells. Cancer Cell 2017; 31: 110\u2013126.","journal-title":"Cancer Cell"},{"key":"BFsigtrans201644_CR39","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1038\/nm.4035","volume":"22","author":"Z Cao","year":"2016","unstructured":"Cao Z, Lis R, Ginsberg M, Chavez D, Shido K, Rabbany SY et al. Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis. Nat Med 2016; 22: 154\u2013162.","journal-title":"Nat Med"},{"key":"BFsigtrans201644_CR40","doi-asserted-by":"publisher","first-page":"10371","DOI":"10.1073\/pnas.0909374107","volume":"107","author":"S Hoehme","year":"2010","unstructured":"Hoehme S, Brulport M, Bauer A, Bedawy E, Schormann W, Hermes M et al. Prediction and validation of cell alignment along microvessels as order principle to restore tissue architecture in liver regeneration. Proc Natl Acad Sci USA 2010; 107: 10371\u201310376.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsigtrans201644_CR41","doi-asserted-by":"publisher","first-page":"2286","DOI":"10.1158\/0008-5472.CAN-10-3367","volume":"71","author":"Z Cao","year":"2011","unstructured":"Cao Z, Fan-Minogue H, Bellovin DI, Yevtodiyenko A, Arzeno J, Yang Q et al. MYC phosphorylation, activation, and tumorigenic potential in hepatocellular carcinoma are regulated by HMG-CoA reductase. Cancer Res 2011; 71: 2286\u20132297.","journal-title":"Cancer Res"},{"key":"BFsigtrans201644_CR42","doi-asserted-by":"publisher","first-page":"s17","DOI":"10.1161\/ATVBAHA.107.160218","volume":"28","author":"GA Zimmerman","year":"2008","unstructured":"Zimmerman GA, Weyrich AS . Signal-dependent protein synthesis by activated platelets: new pathways to altered phenotype and function. Arterioscler Thromb Vasc Biol 2008; 28: s17\u2013s24.","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"BFsigtrans201644_CR43","doi-asserted-by":"publisher","first-page":"3332","DOI":"10.1172\/JCI26720","volume":"115","author":"L Pang","year":"2005","unstructured":"Pang L, Weiss MJ, Poncz M . Megakaryocyte biology and related disorders. J Clin Invest 2005; 115: 3332\u20133338.","journal-title":"J Clin Invest"},{"key":"BFsigtrans201644_CR44","doi-asserted-by":"publisher","first-page":"2368","DOI":"10.1161\/ATVBAHA.110.217281","volume":"30","author":"CC Bertozzi","year":"2010","unstructured":"Bertozzi CC, Hess PR, Kahn ML . Platelets: covert regulators of lymphatic development. Arterioscler Thromb Vasc Biol 2010; 30: 2368\u20132371.","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"BFsigtrans201644_CR45","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/nm1400","volume":"12","author":"DK Jin","year":"2006","unstructured":"Jin DK, Shido K, Kopp HG, Petit I, Shmelkov SV, Young LM et al. Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4+ hemangiocytes. Nat Med 2006; 12: 557\u2013567.","journal-title":"Nat Med"},{"key":"BFsigtrans201644_CR46","doi-asserted-by":"publisher","first-page":"2945","DOI":"10.1073\/pnas.1012531108","volume":"108","author":"K Furrer","year":"2011","unstructured":"Furrer K, Rickenbacher A, Tian Y, Jochum W, Bittermann AG, Kach A et al. Serotonin reverts age-related capillarization and failure of regeneration in the liver through a VEGF-dependent pathway. Proc Natl Acad Sci USA 2011; 108: 2945\u20132950.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsigtrans201644_CR47","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1038\/nm1780","volume":"14","author":"PA Lang","year":"2008","unstructured":"Lang PA, Contaldo C, Georgiev P, El-Badry AM, Recher M, Kurrer M et al. Aggravation of viral hepatitis by platelet-derived serotonin. Nat Med 2008; 14: 756\u2013761.","journal-title":"Nat Med"},{"key":"BFsigtrans201644_CR48","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1038\/nature04478","volume":"438","author":"P Carmeliet","year":"2005","unstructured":"Carmeliet P . Angiogenesis in life, disease and medicine. Nature 2005; 438: 932\u2013936.","journal-title":"Nature"},{"key":"BFsigtrans201644_CR49","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1038\/nm0603-669","volume":"9","author":"N Ferrara","year":"2003","unstructured":"Ferrara N, Gerber HP, LeCouter J . The biology of VEGF and its receptors. Nat Med 2003; 9: 669\u2013676.","journal-title":"Nat Med"},{"key":"BFsigtrans201644_CR50","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.cell.2005.10.036","volume":"124","author":"M Grunewald","year":"2006","unstructured":"Grunewald M, Avraham I, Dor Y, Bachar-Lustig E, Itin A, Jung S et al. VEGF-induced adult neovascularization: recruitment, retention, and role of accessory cells. Cell 2006; 124: 175\u2013189.","journal-title":"Cell"},{"key":"BFsigtrans201644_CR51","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1038\/nrc2524","volume":"8","author":"C Fischer","year":"2008","unstructured":"Fischer C, Mazzone M, Jonckx B, Carmeliet P . FLT1 and its ligands VEGFB and PlGF: drug targets for anti-angiogenic therapy? Nat Rev Cancer 2008; 8: 942\u2013956.","journal-title":"Nat Rev Cancer"},{"key":"BFsigtrans201644_CR52","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1038\/nature04186","volume":"438","author":"RN Kaplan","year":"2005","unstructured":"Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 2005; 438: 820\u2013827.","journal-title":"Nature"},{"key":"BFsigtrans201644_CR53","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1038\/nature10085","volume":"474","author":"JA Stefater 3rd","year":"2011","unstructured":"Stefater JA 3rd, Lewkowich I, Rao S, Mariggi G, Carpenter AC, Burr AR et al. Regulation of angiogenesis by a non-canonical Wnt-Flt1 pathway in myeloid cells. Nature 2011; 474: 511\u2013515.","journal-title":"Nature"},{"key":"BFsigtrans201644_CR54","doi-asserted-by":"crossref","first-page":"3015","DOI":"10.1242\/dev.126.13.3015","volume":"126","author":"GH Fong","year":"1999","unstructured":"Fong GH, Zhang L, Bryce DM, Peng J . Increased hemangioblast commitment, not vascular disorganization, is the primary defect in flt-1 knock-out mice. Development 1999; 126: 3015\u20133025.","journal-title":"Development"},{"key":"BFsigtrans201644_CR55","doi-asserted-by":"publisher","first-page":"15735","DOI":"10.1073\/pnas.0610444104","volume":"104","author":"Z Miao","year":"2007","unstructured":"Miao Z, Luker KE, Summers BC, Berahovich R, Bhojani MS, Rehemtulla A et al. CXCR7 (RDC1) promotes breast and lung tumor growth in vivo and is expressed on tumor-associated vasculature. Proc Natl Acad Sci USA 2007; 104: 15735\u201315740.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsigtrans201644_CR56","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1002\/dvdy.22549","volume":"240","author":"S Yu","year":"2011","unstructured":"Yu S, Crawford D, Tsuchihashi T, Behrens TW, Srivastava D . The chemokine receptor CXCR7 functions to regulate cardiac valve remodeling. Dev Dyn 2011; 240: 384\u2013393.","journal-title":"Dev Dyn"},{"key":"BFsigtrans201644_CR57","doi-asserted-by":"publisher","first-page":"14759","DOI":"10.1073\/pnas.0702229104","volume":"104","author":"F Sierro","year":"2007","unstructured":"Sierro F, Biben C, Martinez-Munoz L, Mellado M, Ransohoff RM, Li M et al. Disrupted cardiac development but normal hematopoiesis in mice deficient in the second CXCL12\/SDF-1 receptor, CXCR7. Proc Natl Acad Sci USA 2007; 104: 14759\u201314764.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsigtrans201644_CR58","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1038\/nature09002","volume":"465","author":"Y Wang","year":"2010","unstructured":"Wang Y, Nakayama M, Pitulescu ME, Schmidt TS, Bochenek ML, Sakakibara A et al. Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis. Nature 2010; 465: 483\u2013486.","journal-title":"Nature"},{"key":"BFsigtrans201644_CR59","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/nature13146","volume":"507","author":"SK Ramasamy","year":"2014","unstructured":"Ramasamy SK, Kusumbe AP, Wang L, Adams RH . Endothelial Notch activity promotes angiogenesis and osteogenesis in bone. Nature 2014; 507: 376\u2013380.","journal-title":"Nature"},{"issue":"Suppl 1","key":"BFsigtrans201644_CR60","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1002\/stem.5530140715","volume":"14","author":"AL Gurney","year":"1996","unstructured":"Gurney AL, de Sauvage FJ . Dissection of c-Mpl and thrombopoietin function: studies of knockout mice and receptor signal transduction. Stem Cells 1996; 14 (Suppl 1): 116\u2013123.","journal-title":"Stem Cells"},{"key":"BFsigtrans201644_CR61","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1016\/S0002-9440(10)63522-5","volume":"163","author":"C Yu","year":"2003","unstructured":"Yu C, Wang F, Jin C, Huang X, Miller DL, Basilico C et al. Role of fibroblast growth factor type 1 and 2 in carbon tetrachloride-induced hepatic injury and fibrogenesis. Am J Pathol 2003; 163: 1653\u20131662.","journal-title":"Am J Pathol"},{"key":"BFsigtrans201644_CR62","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1038\/nm740","volume":"8","author":"K Hattori","year":"2002","unstructured":"Hattori K, Heissig B, Wu Y, Dias S, Tejada R, Ferris B et al. Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment. Nat Med 2002; 8: 841\u2013849.","journal-title":"Nat Med"},{"key":"BFsigtrans201644_CR63","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1038\/ncb2108","volume":"12","author":"H Kobayashi","year":"2010","unstructured":"Kobayashi H, Butler JM, O'Donnell R, Kobayashi M, Ding BS, Bonner B et al. Angiocrine factors from Akt-activated endothelial cells balance self-renewal and differentiation of haematopoietic stem cells. Nat Cell Biol 2010; 12: 1046\u20131056.","journal-title":"Nat Cell Biol"},{"key":"BFsigtrans201644_CR64","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1182\/blood.V88.3.803.803","volume":"88","author":"K Carver-Moore","year":"1996","unstructured":"Carver-Moore K, Broxmeyer HE, Luoh SM, Cooper S, Peng J, Burstein SA et al. Low levels of erythroid and myeloid progenitors in thrombopoietin-and c-mpl-deficient mice. Blood 1996; 88: 803\u2013808.","journal-title":"Blood"},{"key":"BFsigtrans201644_CR65","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.it.2007.05.007","volume":"28","author":"I Petit","year":"2007","unstructured":"Petit I, Jin D, Rafii S . The SDF-1-CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis. Trends Immunol 2007; 28: 299\u2013307.","journal-title":"Trends Immunol"},{"key":"BFsigtrans201644_CR66","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1002\/dvg.20387","volume":"46","author":"H Gerrits","year":"2008","unstructured":"Gerrits H, van Ingen Schenau DS, Bakker NE, van Disseldorp AJ, Strik A, Hermens LS et al. Early postnatal lethality and cardiovascular defects in CXCR7-deficient mice. Genesis 2008; 46: 235\u2013245.","journal-title":"Genesis"},{"key":"BFsigtrans201644_CR67","doi-asserted-by":"publisher","first-page":"4283","DOI":"10.1074\/jbc.M707465200","volume":"283","author":"J Wang","year":"2008","unstructured":"Wang J, Shiozawa Y, Wang Y, Jung Y, Pienta KJ, Mehra R et al. The role of CXCR7\/RDC1 as a chemokine receptor for CXCL12\/SDF-1 in prostate cancer. J Biol Chem 2008; 283: 4283\u20134294.","journal-title":"J Biol Chem"},{"key":"BFsigtrans201644_CR68","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1093\/toxsci\/kfq366","volume":"120","author":"T Kato","year":"2011","unstructured":"Kato T, Ito Y, Hosono K, Suzuki T, Tamaki H, Minamino T et al. Vascular endothelial growth factor receptor-1 signaling promotes liver repair through restoration of liver microvasculature after acetaminophen hepatotoxicity. Toxicol Sci 2011; 120: 218\u2013229.","journal-title":"Toxicol Sci"}],"container-title":["Signal Transduction and Targeted Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/sigtrans201644.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/sigtrans201644","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/sigtrans201644.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T16:16:26Z","timestamp":1671725786000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/sigtrans201644"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,17]]},"references-count":68,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,4,28]]}},"alternative-id":["BFsigtrans201644"],"URL":"https:\/\/doi.org\/10.1038\/sigtrans.2016.44","relation":{},"ISSN":["2059-3635"],"issn-type":[{"value":"2059-3635","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,17]]},"assertion":[{"value":"26 November 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 December 2016","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 December 2016","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 February 2017","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"16044"}}