{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T15:29:02Z","timestamp":1776439742832,"version":"3.51.2"},"reference-count":66,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T00:00:00Z","timestamp":1655683200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T00:00:00Z","timestamp":1655683200000},"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":["Nat Metab"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Angiogenesis, the process by which endothelial cells (ECs) form new blood vessels from existing ones, is intimately linked to the tissue\u2019s metabolic milieu and often occurs at nutrient-deficient sites. However, ECs rely on sufficient metabolic resources to support growth and proliferation. How endothelial nutrient acquisition and usage are regulated is unknown. Here we show that these processes are instructed by Yes-associated protein 1 (YAP)\/WW domain-containing transcription regulator 1 (WWTR1\/TAZ)-transcriptional enhanced associate domain (TEAD): a transcriptional module whose function is highly responsive to changes in the tissue environment. ECs lacking YAP\/TAZ or their transcriptional partners, TEAD1, 2 and 4 fail to divide, resulting in stunted vascular growth in mice. Conversely, activation of TAZ, the more abundant paralogue in ECs, boosts proliferation, leading to vascular hyperplasia. We find that YAP\/TAZ promote angiogenesis by fuelling nutrient-dependent mTORC1 signalling. By orchestrating the transcription of a repertoire of cell-surface transporters, including the large neutral amino acid transporter SLC7A5, YAP\/TAZ-TEAD stimulate the import of amino acids and other essential nutrients, thereby enabling mTORC1 activation. Dissociating mTORC1 from these nutrient inputs\u2014elicited by the loss of Rag GTPases\u2014inhibits mTORC1 activity and prevents YAP\/TAZ-dependent vascular growth. Together, these findings define a pivotal role for YAP\/TAZ-TEAD in controlling endothelial mTORC1 and illustrate the essentiality of coordinated nutrient fluxes in the vasculature.<\/jats:p>","DOI":"10.1038\/s42255-022-00584-y","type":"journal-article","created":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T16:07:21Z","timestamp":1655741241000},"page":"672-682","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":97,"title":["A YAP\/TAZ-TEAD signalling module links endothelial nutrient acquisition to angiogenic growth"],"prefix":"10.1038","volume":"4","author":[{"given":"Yu Ting","family":"Ong","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4577-8620","authenticated-orcid":false,"given":"Jorge","family":"Andrade","sequence":"additional","affiliation":[]},{"given":"Max","family":"Armbruster","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8645-2002","authenticated-orcid":false,"given":"Chenyue","family":"Shi","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7851-7446","authenticated-orcid":false,"given":"Marco","family":"Castro","sequence":"additional","affiliation":[]},{"given":"Ana S. H.","family":"Costa","sequence":"additional","affiliation":[]},{"given":"Toshiya","family":"Sugino","sequence":"additional","affiliation":[]},{"given":"Guy","family":"Eelen","sequence":"additional","affiliation":[]},{"given":"Barbara","family":"Zimmermann","sequence":"additional","affiliation":[]},{"given":"Kerstin","family":"Wilhelm","sequence":"additional","affiliation":[]},{"given":"Joseph","family":"Lim","sequence":"additional","affiliation":[]},{"given":"Shuichi","family":"Watanabe","sequence":"additional","affiliation":[]},{"given":"Stefan","family":"Guenther","sequence":"additional","affiliation":[]},{"given":"Andre","family":"Schneider","sequence":"additional","affiliation":[]},{"given":"Francesca","family":"Zanconato","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9528-8822","authenticated-orcid":false,"given":"Manuel","family":"Kaulich","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2890-4645","authenticated-orcid":false,"given":"Duojia","family":"Pan","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6165-4804","authenticated-orcid":false,"given":"Thomas","family":"Braun","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3030-0384","authenticated-orcid":false,"given":"Holger","family":"Gerhardt","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3806-6799","authenticated-orcid":false,"given":"Alejo","family":"Efeyan","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7961-1821","authenticated-orcid":false,"given":"Peter","family":"Carmeliet","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1600-3092","authenticated-orcid":false,"given":"Stefano","family":"Piccolo","sequence":"additional","affiliation":[]},{"given":"Ana Rita","family":"Grosso","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5689-0036","authenticated-orcid":false,"given":"Michael","family":"Potente","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2022,6,20]]},"reference":[{"key":"584_CR1","doi-asserted-by":"publisher","first-page":"eaal2379","DOI":"10.1126\/science.aal2379","volume":"357","author":"HG Augustin","year":"2017","unstructured":"Augustin, H. G. & Koh, G. Y. Organotypic vasculature: from descriptive heterogeneity to functional pathophysiology. Science 357, eaal2379 (2017).","journal-title":"Science"},{"key":"584_CR2","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1038\/nrm.2017.36","volume":"18","author":"M Potente","year":"2017","unstructured":"Potente, M. & Makinen, T. Vascular heterogeneity and specialization in development and disease. Nat. Rev. Mol. Cell Biol. 18, 477\u2013494 (2017).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"584_CR3","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/nature22379","volume":"546","author":"W Palm","year":"2017","unstructured":"Palm, W. & Thompson, C. B. Nutrient acquisition strategies of mammalian cells. Nature 546, 234\u2013242 (2017).","journal-title":"Nature"},{"key":"584_CR4","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1016\/j.cmet.2019.08.011","volume":"30","author":"X Li","year":"2019","unstructured":"Li, X., Sun, X. & Carmeliet, P. Hallmarks of endothelial cell metabolism in health and disease. Cell Metab. 30, 414\u2013433 (2019).","journal-title":"Cell Metab."},{"key":"584_CR5","doi-asserted-by":"publisher","first-page":"3441","DOI":"10.1172\/JCI93825","volume":"127","author":"J Kim","year":"2017","unstructured":"Kim, J. et al. YAP\/TAZ regulates sprouting angiogenesis and vascular barrier maturation. J. Clin. Invest. 127, 3441\u20133461 (2017).","journal-title":"J. Clin. Invest."},{"key":"584_CR6","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1016\/j.devcel.2017.08.002","volume":"42","author":"X Wang","year":"2017","unstructured":"Wang, X. et al. YAP\/TAZ orchestrate VEGF signaling during developmental angiogenesis. Dev. Cell 42, 462\u2013478.e467 (2017).","journal-title":"Dev. Cell"},{"key":"584_CR7","doi-asserted-by":"publisher","first-page":"10918","DOI":"10.1073\/pnas.1704030114","volume":"114","author":"M Sakabe","year":"2017","unstructured":"Sakabe, M. et al. YAP\/TAZ-CDC42 signaling regulates vascular tip cell migration. Proc. Natl Acad. Sci. USA 114, 10918\u201310923 (2017).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"584_CR8","doi-asserted-by":"publisher","unstructured":"Neto, F. et al. YAP and TAZ regulate adherens junction dynamics and endothelial cell distribution during vascular development. eLife https:\/\/doi.org\/10.7554\/eLife.31037 (2018).","DOI":"10.7554\/eLife.31037"},{"key":"584_CR9","doi-asserted-by":"publisher","first-page":"e50770","DOI":"10.7554\/eLife.50770","volume":"9","author":"KK Sivaraj","year":"2020","unstructured":"Sivaraj, K. K. et al. YAP1 and TAZ negatively control bone angiogenesis by limiting hypoxia-inducible factor signaling in endothelial cells. eLife 9, e50770 (2020).","journal-title":"eLife"},{"key":"584_CR10","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1083\/jcb.201501089","volume":"211","author":"C Giampietro","year":"2015","unstructured":"Giampietro, C. et al. The actin-binding protein EPS8 binds VE-cadherin and modulates YAP localization and signaling. J. Cell Biol. 211, 1177\u20131192 (2015).","journal-title":"J. Cell Biol."},{"key":"584_CR11","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1016\/j.devcel.2017.02.019","volume":"40","author":"H Nakajima","year":"2017","unstructured":"Nakajima, H. et al. Flow-dependent endothelial YAP regulation contributes to vessel maintenance. Dev. Cell 40, 523\u2013536.e526 (2017).","journal-title":"Dev. Cell"},{"key":"584_CR12","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1038\/nature20602","volume":"540","author":"L Wang","year":"2016","unstructured":"Wang, L. et al. Integrin-YAP\/TAZ-JNK cascade mediates atheroprotective effect of unidirectional shear flow. Nature 540, 579\u2013582 (2016).","journal-title":"Nature"},{"key":"584_CR13","doi-asserted-by":"publisher","first-page":"11525","DOI":"10.1073\/pnas.1613121113","volume":"113","author":"KC Wang","year":"2016","unstructured":"Wang, K. C. et al. Flow-dependent YAP\/TAZ activities regulate endothelial phenotypes and atherosclerosis. Proc. Natl Acad. Sci. USA 113, 11525\u201311530 (2016).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"584_CR14","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1038\/s41556-018-0142-z","volume":"20","author":"A Totaro","year":"2018","unstructured":"Totaro, A., Panciera, T. & Piccolo, S. YAP\/TAZ upstream signals and downstream responses. Nat. Cell Biol. 20, 888\u2013899 (2018).","journal-title":"Nat. Cell Biol."},{"key":"584_CR15","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.cmet.2018.07.010","volume":"28","author":"JH Koo","year":"2018","unstructured":"Koo, J. H. & Guan, K. L. Interplay between YAP\/TAZ and metabolism. Cell Metab. 28, 196\u2013206 (2018).","journal-title":"Cell Metab."},{"key":"584_CR16","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.ceb.2012.12.006","volume":"25","author":"ER Barry","year":"2013","unstructured":"Barry, E. R. & Camargo, F. D. The Hippo superhighway: signaling crossroads converging on the Hippo\/YAP pathway in stem cells and development. Curr. Opin. Cell Biol. 25, 247\u2013253 (2013).","journal-title":"Curr. Opin. Cell Biol."},{"key":"584_CR17","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/j.devcel.2020.06.025","volume":"54","author":"C Ibar","year":"2020","unstructured":"Ibar, C. & Irvine, K. D. Integration of hippo-YAP signaling with metabolism. Dev. Cell 54, 256\u2013267 (2020).","journal-title":"Dev. Cell"},{"key":"584_CR18","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.devcel.2019.06.003","volume":"50","author":"Y Zheng","year":"2019","unstructured":"Zheng, Y. & Pan, D. The hippo signaling pathway in development and disease. Dev. Cell 50, 264\u2013282 (2019).","journal-title":"Dev. Cell"},{"key":"584_CR19","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/s41580-018-0086-y","volume":"20","author":"IM Moya","year":"2019","unstructured":"Moya, I. M. & Halder, G. Hippo-YAP\/TAZ signalling in organ regeneration and regenerative medicine. Nat. Rev. Mol. Cell Biol. 20, 211\u2013226 (2019).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"584_CR20","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.devcel.2010.06.015","volume":"19","author":"N Zhang","year":"2010","unstructured":"Zhang, N. et al. The Merlin\/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals. Dev. Cell 19, 27\u201338 (2010).","journal-title":"Dev. Cell"},{"key":"584_CR21","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.cell.2014.06.013","volume":"158","author":"L Azzolin","year":"2014","unstructured":"Azzolin, L. et al. YAP\/TAZ incorporation in the beta-catenin destruction complex orchestrates the Wnt response. Cell 158, 157\u2013170 (2014).","journal-title":"Cell"},{"key":"584_CR22","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1038\/nature25739","volume":"554","author":"M Vanlandewijck","year":"2018","unstructured":"Vanlandewijck, M. et al. A molecular atlas of cell types and zonation in the brain vasculature. Nature 554, 475\u2013480 (2018).","journal-title":"Nature"},{"key":"584_CR23","doi-asserted-by":"publisher","first-page":"3177","DOI":"10.1128\/MCB.01759-07","volume":"28","author":"A Sawada","year":"2008","unstructured":"Sawada, A. et al. Redundant roles of Tead1 and Tead2 in notochord development and the regulation of cell proliferation and survival. Mol. Cell. Biol. 28, 3177\u20133189 (2008).","journal-title":"Mol. Cell. Biol."},{"key":"584_CR24","doi-asserted-by":"publisher","first-page":"1962","DOI":"10.1101\/gad.1664408","volume":"22","author":"B Zhao","year":"2008","unstructured":"Zhao, B. et al. TEAD mediates YAP-dependent gene induction and growth control. Genes Dev. 22, 1962\u20131971 (2008).","journal-title":"Genes Dev."},{"key":"584_CR25","doi-asserted-by":"publisher","first-page":"13355","DOI":"10.1074\/jbc.M900843200","volume":"284","author":"H Zhang","year":"2009","unstructured":"Zhang, H. et al. TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition. J. Biol. Chem. 284, 13355\u201313362 (2009).","journal-title":"J. Biol. Chem."},{"key":"584_CR26","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/s42255-019-0038-7","volume":"1","author":"AJ Valvezan","year":"2019","unstructured":"Valvezan, A. J. & Manning, B. D. Molecular logic of mTORC1 signalling as a metabolic rheostat. Nat. Metab. 1, 321\u2013333 (2019).","journal-title":"Nat. Metab."},{"key":"584_CR27","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1038\/s41568-018-0074-8","volume":"18","author":"D Mossmann","year":"2018","unstructured":"Mossmann, D., Park, S. & Hall, M. N. mTOR signalling and cellular metabolism are mutual determinants in cancer. Nat. Rev. Cancer 18, 744\u2013757 (2018).","journal-title":"Nat. Rev. Cancer"},{"key":"584_CR28","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","volume":"168","author":"RA Saxton","year":"2017","unstructured":"Saxton, R. A. & Sabatini, D. M. mTOR signaling in growth, metabolism, and disease. Cell 168, 960\u2013976 (2017).","journal-title":"Cell"},{"key":"584_CR29","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/j.cell.2008.11.044","volume":"136","author":"P Nicklin","year":"2009","unstructured":"Nicklin, P. et al. Bidirectional transport of amino acids regulates mTOR and autophagy. Cell 136, 521\u2013534 (2009).","journal-title":"Cell"},{"key":"584_CR30","doi-asserted-by":"publisher","first-page":"1782","DOI":"10.1158\/0008-5472.CAN-14-3745","volume":"75","author":"YD Bhutia","year":"2015","unstructured":"Bhutia, Y. D., Babu, E., Ramachandran, S. & Ganapathy, V. Amino acid transporters in cancer and their relevance to \u2019glutamine addiction\u2019: novel targets for the design of a new class of anticancer drugs. Cancer Res. 75, 1782\u20131788 (2015).","journal-title":"Cancer Res."},{"key":"584_CR31","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.mam.2012.10.007","volume":"34","author":"D Fotiadis","year":"2013","unstructured":"Fotiadis, D., Kanai, Y. & Palac\u00edn, M. The SLC3 and SLC7 families of amino acid transporters. Mol. Asp. Med 34, 139\u2013158 (2013).","journal-title":"Mol. Asp. Med"},{"key":"584_CR32","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1038\/cr.2015.140","volume":"25","author":"CG Hansen","year":"2015","unstructured":"Hansen, C. G., Ng, Y. L., Lam, W. L., Plouffe, S. W. & Guan, K. L. The Hippo pathway effectors YAP and TAZ promote cell growth by modulating amino acid signaling to mTORC1. Cell Res 25, 1299\u20131313 (2015).","journal-title":"Cell Res"},{"key":"584_CR33","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1002\/hep.28223","volume":"63","author":"YY Park","year":"2016","unstructured":"Park, Y. Y. et al. Yes-associated protein 1 and transcriptional coactivator with PDZ-binding motif activate the mammalian target of rapamycin complex 1 pathway by regulating amino acid transporters in hepatocellular carcinoma. Hepatology 63, 159\u2013172 (2016).","journal-title":"Hepatology"},{"key":"584_CR34","doi-asserted-by":"publisher","first-page":"eaan4667","DOI":"10.1126\/scisignal.aan4667","volume":"10","author":"DN Edwards","year":"2017","unstructured":"Edwards, D. N. et al. The receptor tyrosine kinase EphA2 promotes glutamine metabolism in tumors by activating the transcriptional coactivators YAP and TAZ. Sci. Signal 10, eaan4667 (2017).","journal-title":"Sci. Signal"},{"key":"584_CR35","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1038\/ncb3216","volume":"17","author":"F Zanconato","year":"2015","unstructured":"Zanconato, F. et al. Genome-wide association between YAP\/TAZ\/TEAD and AP-1 at enhancers drives oncogenic growth. Nat. Cell Biol. 17, 1218\u20131227 (2015).","journal-title":"Nat. Cell Biol."},{"key":"584_CR36","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.cell.2010.02.024","volume":"141","author":"Y Sancak","year":"2010","unstructured":"Sancak, Y. et al. Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 141, 290\u2013303 (2010).","journal-title":"Cell"},{"key":"584_CR37","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1038\/ncb1753","volume":"10","author":"E Kim","year":"2008","unstructured":"Kim, E., Goraksha-Hicks, P., Li, L., Neufeld, T. P. & Guan, K. L. Regulation of TORC1 by Rag GTPases in nutrient response. Nat. Cell Biol. 10, 935\u2013945 (2008).","journal-title":"Nat. Cell Biol."},{"key":"584_CR38","doi-asserted-by":"publisher","first-page":"1496","DOI":"10.1126\/science.1157535","volume":"320","author":"Y Sancak","year":"2008","unstructured":"Sancak, Y. et al. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 320, 1496\u20131501 (2008).","journal-title":"Science"},{"key":"584_CR39","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.devcel.2014.03.017","volume":"29","author":"A Efeyan","year":"2014","unstructured":"Efeyan, A. et al. RagA, but not RagB, is essential for embryonic development and adult mice. Dev. Cell 29, 321\u2013329 (2014).","journal-title":"Dev. Cell"},{"key":"584_CR40","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1101\/gad.340661.120","volume":"34","author":"B King","year":"2020","unstructured":"King, B., Araki, J., Palm, W. & Thompson, C. B. Yap\/Taz promote the scavenging of extracellular nutrients through macropinocytosis. Genes Dev. 34, 1345\u20131358 (2020).","journal-title":"Genes Dev."},{"key":"584_CR41","doi-asserted-by":"publisher","first-page":"2321","DOI":"10.15252\/embj.201796436","volume":"36","author":"B Kim","year":"2017","unstructured":"Kim, B., Li, J., Jang, C. & Arany, Z. Glutamine fuels proliferation but not migration of endothelial cells. EMBO J. 36, 2321\u20132333 (2017).","journal-title":"EMBO J."},{"key":"584_CR42","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1038\/s41556-021-00637-6","volume":"23","author":"J Andrade","year":"2021","unstructured":"Andrade, J. et al. Control of endothelial quiescence by FOXO-regulated metabolites. Nat. Cell Biol. 23, 413\u2013423 (2021).","journal-title":"Nat. Cell Biol."},{"key":"584_CR43","doi-asserted-by":"publisher","first-page":"2747","DOI":"10.1101\/gad.1602907","volume":"21","author":"B Zhao","year":"2007","unstructured":"Zhao, B. et al. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev. 21, 2747\u20132761 (2007).","journal-title":"Genes Dev."},{"key":"584_CR44","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1038\/ncb1748","volume":"10","author":"X Varelas","year":"2008","unstructured":"Varelas, X. et al. TAZ controls Smad nucleocytoplasmic shuttling and regulates human embryonic stem-cell self-renewal. Nat. Cell Biol. 10, 837\u2013848 (2008).","journal-title":"Nat. Cell Biol."},{"key":"584_CR45","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/nature09917","volume":"473","author":"V Guarani","year":"2011","unstructured":"Guarani, V. et al. Acetylation-dependent regulation of endothelial Notch signalling by the SIRT1 deacetylase. Nature 473, 234\u2013238 (2011).","journal-title":"Nature"},{"key":"584_CR46","doi-asserted-by":"publisher","first-page":"2856","DOI":"10.1038\/nprot.2006.468","volume":"1","author":"A Shevchenko","year":"2006","unstructured":"Shevchenko, A., Tomas, H., Havlis, J., Olsen, J. V. & Mann, M. In-gel digestion for mass spectrometric characterization of proteins and proteomes. Nat. Protoc. 1, 2856\u20132860 (2006).","journal-title":"Nat. Protoc."},{"key":"584_CR47","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1021\/ac026117i","volume":"75","author":"J Rappsilber","year":"2003","unstructured":"Rappsilber, J., Ishihama, Y. & Mann, M. Stop and go extraction tips for matrix-assisted laser desorption\/ionization, nanoelectrospray, and LC\/MS sample pretreatment in proteomics. Anal. Chem. 75, 663\u2013670 (2003).","journal-title":"Anal. Chem."},{"key":"584_CR48","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1038\/nbt.1511","volume":"26","author":"J Cox","year":"2008","unstructured":"Cox, J. & Mann, M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol. 26, 1367\u20131372 (2008).","journal-title":"Nat. Biotechnol."},{"key":"584_CR49","doi-asserted-by":"publisher","first-page":"1794","DOI":"10.1021\/pr101065j","volume":"10","author":"J Cox","year":"2011","unstructured":"Cox, J. et al. Andromeda: a peptide search engine integrated into the MaxQuant environment. J. Proteome Res. 10, 1794\u20131805 (2011).","journal-title":"J. Proteome Res."},{"key":"584_CR50","doi-asserted-by":"publisher","first-page":"2513","DOI":"10.1074\/mcp.M113.031591","volume":"13","author":"J Cox","year":"2014","unstructured":"Cox, J. et al. Accurate proteome-wide label-free quantification by delayed normalization and maximal peptide ratio extraction, termed MaxLFQ. Mol. Cell Proteom. 13, 2513\u20132526 (2014).","journal-title":"Mol. Cell Proteom."},{"key":"584_CR51","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/nmeth.3901","volume":"13","author":"S Tyanova","year":"2016","unstructured":"Tyanova, S. et al. The Perseus computational platform for comprehensive analysis of (prote)omics data. Nat. Methods 13, 731\u2013740 (2016).","journal-title":"Nat. Methods"},{"key":"584_CR52","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.ymeth.2013.06.027","volume":"63","author":"MP Davis","year":"2013","unstructured":"Davis, M. P., van Dongen, S., Abreu-Goodger, C., Bartonicek, N. & Enright, A. J. Kraken: a set of tools for quality control and analysis of high-throughput sequence data. Methods 63, 41\u201349 (2013).","journal-title":"Methods"},{"key":"584_CR53","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15\u201321 (2013).","journal-title":"Bioinformatics"},{"key":"584_CR54","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545\u201315550 (2005).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"584_CR55","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1038\/ng1180","volume":"34","author":"VK Mootha","year":"2003","unstructured":"Mootha, V. K. et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat. Genet. 34, 267\u2013273 (2003).","journal-title":"Nat. Genet."},{"key":"584_CR56","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-9-r137","volume":"9","author":"Y Zhang","year":"2008","unstructured":"Zhang, Y. et al. Model-based analysis of ChIP\u2013seq (MACS). Genome Biol. 9, R137 (2008).","journal-title":"Genome Biol."},{"key":"584_CR57","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.molcel.2010.05.004","volume":"38","author":"S Heinz","year":"2010","unstructured":"Heinz, S. et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38, 576\u2013589 (2010).","journal-title":"Mol. Cell"},{"key":"584_CR58","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1126\/science.aat0778","volume":"364","author":"R Lim","year":"2019","unstructured":"Lim, R. et al. Deubiquitinase USP10 regulates Notch signaling in the endothelium. Science 364, 188\u2013193 (2019).","journal-title":"Science"},{"key":"584_CR59","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/s41586-018-0466-7","volume":"561","author":"G Eelen","year":"2018","unstructured":"Eelen, G. et al. Role of glutamine synthetase in angiogenesis beyond glutamine synthesis. Nature 561, 63\u201369 (2018).","journal-title":"Nature"},{"key":"584_CR60","doi-asserted-by":"publisher","first-page":"2334","DOI":"10.15252\/embj.201695518","volume":"36","author":"H Huang","year":"2017","unstructured":"Huang, H. et al. Role of glutamine and interlinked asparagine metabolism in vessel formation. EMBO J. 36, 2334\u20132352 (2017).","journal-title":"EMBO J."},{"key":"584_CR61","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/bs.mie.2015.05.016","volume":"561","author":"GM Mackay","year":"2015","unstructured":"Mackay, G. M., Zheng, L., van den Broek, N. J. & Gottlieb, E. Analysis of cell metabolism using LC-MS and isotope tracers. Methods Enzymol. 561, 171\u2013196 (2015).","journal-title":"Methods Enzymol."},{"key":"584_CR62","doi-asserted-by":"publisher","first-page":"e1006600","DOI":"10.1371\/journal.pgen.1006600","volume":"13","author":"S Joshi","year":"2017","unstructured":"Joshi, S. et al. TEAD transcription factors are required for normal primary myoblast differentiation in vitro and muscle regeneration in vivo. PLoS Genet. 13, e1006600 (2017).","journal-title":"PLoS Genet."},{"key":"584_CR63","doi-asserted-by":"publisher","first-page":"e89547","DOI":"10.1371\/journal.pone.0089547","volume":"9","author":"N Poncet","year":"2014","unstructured":"Poncet, N. et al. The catalytic subunit of the system L1 amino acid transporter (slc7a5) facilitates nutrient signalling in mouse skeletal muscle. PLoS ONE 9, e89547 (2014).","journal-title":"PLoS ONE"},{"key":"584_CR64","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1038\/ni.2556","volume":"14","author":"LV Sinclair","year":"2013","unstructured":"Sinclair, L. V. et al. Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation. Nat. Immunol. 14, 500\u2013508 (2013).","journal-title":"Nat. Immunol."},{"key":"584_CR65","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1002\/dvg.20367","volume":"46","author":"S Claxton","year":"2008","unstructured":"Claxton, S. et al. Efficient, inducible Cre-recombinase activation in vascular endothelium. Genesis 46, 74\u201380 (2008).","journal-title":"Genesis"},{"key":"584_CR66","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/nature16498","volume":"529","author":"K Wilhelm","year":"2016","unstructured":"Wilhelm, K. et al. FOXO1 couples metabolic activity and growth state in the vascular endothelium. Nature 529, 216\u2013220 (2016).","journal-title":"Nature"}],"container-title":["Nature Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42255-022-00584-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42255-022-00584-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42255-022-00584-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T09:06:53Z","timestamp":1669367213000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42255-022-00584-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,20]]},"references-count":66,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["584"],"URL":"https:\/\/doi.org\/10.1038\/s42255-022-00584-y","relation":{},"ISSN":["2522-5812"],"issn-type":[{"value":"2522-5812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,20]]},"assertion":[{"value":"18 February 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 June 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}