{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T13:52:57Z","timestamp":1791726777064,"version":"4.3.4"},"reference-count":77,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T00:00:00Z","timestamp":1566172800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T00:00:00Z","timestamp":1566172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01NS092521"],"award-info":[{"award-number":["P01NS092521"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL094326"],"award-info":[{"award-number":["R01HL094326"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS100949"],"award-info":[{"award-number":["R01NS100949"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F30 HL140871"],"award-info":[{"award-number":["F30 HL140871"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 GM007171"],"award-info":[{"award-number":["T32 GM007171"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 CA14599"],"award-info":[{"award-number":["P30 CA14599"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["F30NS100252"],"award-info":[{"award-number":["F30NS100252"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"William and Judith Davis Fund in Neurovascular Surgery Research"},{"name":"Safadi Translational Fellowship"},{"DOI":"10.13039\/100008140","name":"University of Chicago Pritzker School of Medicine","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008140","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The China Scholarship Council"},{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9liuksen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010129","name":"Maud Kuistilan Muistos\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004756","name":"Emil Aaltosen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004756","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["acta neuropathol commun"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1186\/s40478-019-0789-0","type":"journal-article","created":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T08:02:43Z","timestamp":1566201763000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Transcriptome clarifies mechanisms of lesion genesis versus progression in models of Ccm3 cerebral cavernous malformations"],"prefix":"10.1186","volume":"7","author":[{"given":"Janne","family":"Koskim\u00e4ki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongdong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laleh","family":"Saadat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhonda","family":"Lightle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean P.","family":"Polster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juli\u00e1n","family":"Carri\u00f3n-Penagos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se\u00e1n B.","family":"Lyne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussein A.","family":"Zeineddine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changbin","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1300-6845","authenticated-orcid":false,"given":"Robert","family":"Shenkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharbel","family":"Romanos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Avner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhinav","family":"Srinath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Detter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Snellings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"Lopez-Ramirez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Fonseca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan T.","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Faber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Andrade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Ginsberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark L.","family":"Kahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas A.","family":"Marchuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romuald","family":"Girard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Issam A.","family":"Awad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,8,19]]},"reference":[{"key":"789_CR1","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1097\/00006123-199901000-00020","volume":"44","author":"SI Abdulrauf","year":"1999","unstructured":"Abdulrauf SI, Kaynar MY, Awad IA (1999) A comparison of the clinical profile of cavernous malformations with and without associated venous malformations. Neurosurgery 44:41\u201346","journal-title":"Neurosurgery"},{"key":"789_CR2","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1093\/neuros\/nyx091","volume":"80","author":"A Akers","year":"2017","unstructured":"Akers A, Al-Shahi Salman R, Awad IA, Dahlem K, Flemming K, Hart B et al (2017) Synopsis of guidelines for the clinical management of cerebral cavernous malformations: consensus recommendations based on systematic literature review by the angioma alliance scientific advisory board clinical experts panel. Neurosurgery 80:665\u2013680","journal-title":"Neurosurgery"},{"key":"789_CR3","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1083\/jcb.201308031","volume":"205","author":"LB Alcaraz","year":"2014","unstructured":"Alcaraz LB, Exposito JY, Chuvin N, Pommier RM, Cluzel C, Martel S et al (2014) Tenascin-X promotes epithelial-to-mesenchymal transition by activating latent TGF-beta. J Cell Biol 205:409\u2013428","journal-title":"J Cell Biol"},{"key":"789_CR4","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/S1474-4422(12)70004-2","volume":"11","author":"R Al-Shahi Salman","year":"2012","unstructured":"Al-Shahi Salman R, Hall JM, Horne MA, Moultrie F, Josephson CB, Bhattacharya JJ et al (2012) Untreated clinical course of cerebral cavernous malformations: a prospective, population-based cohort study. Lancet Neurol 11:217\u2013224","journal-title":"Lancet Neurol"},{"key":"789_CR5","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1038\/nrm1401","volume":"5","author":"FA Barr","year":"2004","unstructured":"Barr FA, Sillje HH, Nigg EA (2004) Polo-like kinases and the orchestration of cell division. Nat Rev Mol Cell Biol 5:429\u2013440","journal-title":"Nat Rev Mol Cell Biol"},{"key":"789_CR6","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1038\/nrm3629","volume":"14","author":"C Bertoli","year":"2013","unstructured":"Bertoli C, Skotheim JM, de Bruin RA (2013) Control of cell cycle transcription during G1 and S phases. Nat Rev Mol Cell Biol 14:518\u2013528","journal-title":"Nat Rev Mol Cell Biol"},{"key":"789_CR7","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/nrc2169","volume":"7","author":"R Boutros","year":"2007","unstructured":"Boutros R, Lobjois V, Ducommun B (2007) CDC25 phosphatases in cancer cells: key players? Good targets? Nat Rev Cancer 7:495\u2013507","journal-title":"Nat Rev Cancer"},{"key":"789_CR8","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/S0090-3019(00)00218-4","volume":"53","author":"L Brunereau","year":"2000","unstructured":"Brunereau L, Levy C, Laberge S, Houtteville J, Labauge P (2000) De novo lesions in familial form of cerebral cavernous malformations: clinical and MR features in 29 non-Hispanic families. Surg Neurol 53:475\u2013482","journal-title":"Surg Neurol"},{"key":"789_CR9","doi-asserted-by":"publisher","first-page":"1791","DOI":"10.1038\/s41467-019-09829-z","volume":"10","author":"EM Chapman","year":"2019","unstructured":"Chapman EM, Lant B, Ohashi Y, Yu B, Schertzberg M, Go C et al (2019) A conserved CCM complex promotes apoptosis non-autonomously by regulating zinc homeostasis. Nat Commun 10:1791","journal-title":"Nat Commun"},{"key":"789_CR10","doi-asserted-by":"publisher","first-page":"G1361","DOI":"10.1152\/ajpgi.00202.2010","volume":"299","author":"JH Chidlow Jr","year":"2010","unstructured":"Chidlow JH Jr, Glawe JD, Alexander JS, Kevil CG (2010) VEGF(1)(6)(4) differentially regulates neutrophil and T cell adhesion through ItgaL- and ItgaM-dependent mechanisms. Am J Physiol Gastrointest Liver Physiol 299:G1361\u2013G1367","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"789_CR11","doi-asserted-by":"crossref","unstructured":"Coleman KE, Bekes M, Chapman JR, Crist SB, Jones MJ, Ueberheide BM et al (2017) SENP8 limits aberrant neddylation of NEDD8 pathway components to promote cullin-RING ubiquitin ligase function. Elife 5;6:e24325","DOI":"10.7554\/eLife.24325.022"},{"key":"789_CR12","unstructured":"Core-team R (2015) R: a language and environment for statistical computing. R Foundation for statistical computing, Vienna, Austria. URL \n                    https:\/\/www.R-project.org\/"},{"key":"789_CR13","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1161\/CIRCRESAHA.118.313970","volume":"123","author":"MR Detter","year":"2018","unstructured":"Detter MR, Snellings DA, Marchuk DA (2018) Cerebral cavernous malformations develop through clonal expansion of mutant endothelial cells. Circ Res 123:1143\u20131151","journal-title":"Circ Res"},{"key":"789_CR14","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1038\/nrm3567","volume":"14","author":"FA Dick","year":"2013","unstructured":"Dick FA, Rubin SM (2013) Molecular mechanisms underlying RB protein function. Nat Rev Mol Cell Biol 14:297\u2013306","journal-title":"Nat Rev Mol Cell Biol"},{"key":"789_CR15","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1038\/nbt1225","volume":"24","author":"RG Fahmy","year":"2006","unstructured":"Fahmy RG, Waldman A, Zhang G, Mitchell A, Tedla N, Cai H et al (2006) Suppression of vascular permeability and inflammation by targeting of the transcription factor c-Jun. Nat Biotechnol 24:856\u2013863","journal-title":"Nat Biotechnol"},{"key":"789_CR16","doi-asserted-by":"publisher","first-page":"1716","DOI":"10.1161\/CIRCRESAHA.118.312680","volume":"122","author":"R Girard","year":"2018","unstructured":"Girard R, Zeineddine HA, Koskim\u00e4ki J, Fam MD, Cao Y, Shi C et al (2018) Plasma biomarkers of inflammation and angiogenesis predict cerebral cavernous malformation symptomatic hemorrhage or lesional growth. Circ Res 122:1716\u20131721","journal-title":"Circ Res"},{"key":"789_CR17","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1242\/dmm.003293","volume":"3","author":"AJ Glading","year":"2010","unstructured":"Glading AJ, Ginsberg MH (2010) Rap1 and its effector KRIT1\/CCM1 regulate beta-catenin signaling. Dis Model Mech 3:73\u201383","journal-title":"Dis Model Mech"},{"key":"789_CR18","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1038\/349132a0","volume":"349","author":"M Glotzer","year":"1991","unstructured":"Glotzer M, Murray AW, Kirschner MW (1991) Cyclin is degraded by the ubiquitin pathway. Nature 349:132\u2013138","journal-title":"Nature"},{"key":"789_CR19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011786","volume":"5","author":"L Goitre","year":"2010","unstructured":"Goitre L, Balzac F, Degani S, Degan P, Marchi S, Pinton P et al (2010) KRIT1 regulates the homeostasis of intracellular reactive oxygen species. PLoS One 5:e11786","journal-title":"PLoS One"},{"key":"789_CR20","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/j.cell.2004.10.019","volume":"119","author":"SJ Goldenberg","year":"2004","unstructured":"Goldenberg SJ, Cascio TC, Shumway SD, Garbutt KC, Liu J, Xiong Y et al (2004) Structure of the Cand1-Cul1-Roc1 complex reveals regulatory mechanisms for the assembly of the multisubunit cullin-dependent ubiquitin ligases. Cell 119:517\u2013528","journal-title":"Cell"},{"key":"789_CR21","doi-asserted-by":"publisher","first-page":"3122","DOI":"10.1038\/sj.onc.1210407","volume":"26","author":"ZG Goldsmith","year":"2007","unstructured":"Goldsmith ZG, Dhanasekaran DN (2007) G protein regulation of MAPK networks. Oncogene 26:3122\u20133142","journal-title":"Oncogene"},{"key":"789_CR22","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1159\/000493293","volume":"49","author":"SK Guo","year":"2018","unstructured":"Guo SK, Shen MF, Yao HW, Liu YS (2018) Enhanced expression of TGFBI promotes the proliferation and migration of glioma cells. Cell Physiol Biochem 49:1097\u20131109","journal-title":"Cell Physiol Biochem"},{"key":"789_CR23","first-page":"ra26","volume":"3","author":"Y He","year":"2010","unstructured":"He Y, Zhang H, Yu L, Gunel M, Boggon TJ, Chen H et al (2010) Stabilization of VEGFR2 signaling by cerebral cavernous malformation 3 is critical for vascular development. Sci Signal 3:ra26","journal-title":"Sci Signal"},{"key":"789_CR24","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/ncb918","volume":"5","author":"M Jackman","year":"2003","unstructured":"Jackman M, Lindon C, Nigg EA, Pines J (2003) Active cyclin B1-Cdk1 first appears on centrosomes in prophase. Nat Cell Biol 5:143\u2013148","journal-title":"Nat Cell Biol"},{"key":"789_CR25","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1007\/s12031-017-0880-6","volume":"61","author":"S Kar","year":"2017","unstructured":"Kar S, Bali KK, Baisantry A, Geffers R, Samii A, Bertalanffy H (2017) Genome-wide sequencing reveals microRNAs downregulated in cerebral cavernous malformations. J Mol Neurosci 61:178\u2013188","journal-title":"J Mol Neurosci"},{"key":"789_CR26","doi-asserted-by":"publisher","first-page":"4","DOI":"10.3389\/neuro.02.004.2008","volume":"1","author":"D Keith","year":"2008","unstructured":"Keith D, El-Husseini A (2008) Excitation control: balancing PSD-95 function at the synapse. Front Mol Neurosci 1:4","journal-title":"Front Mol Neurosci"},{"key":"789_CR27","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1038\/nm.1918","volume":"15","author":"B Kleaveland","year":"2009","unstructured":"Kleaveland B, Zheng X, Liu JJ, Blum Y, Tung JJ, Zou Z et al (2009) Regulation of cardiovascular development and integrity by the heart of glass-cerebral cavernous malformation protein pathway. Nat Med 15:169\u2013176","journal-title":"Nat Med"},{"key":"789_CR28","doi-asserted-by":"crossref","unstructured":"Koskim\u00e4ki J, Girard R, Li Y, Saadat L, Zeineddine HA, Lightle R et al (2019) Comprehensive transcriptome analysis of cerebral cavernous malformation across multiple species and genotypes. JCI Insight 7;4(3):e126167","DOI":"10.1172\/jci.insight.126167"},{"key":"789_CR29","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1083\/jcb.201606055","volume":"217","author":"I Kovacevic","year":"2018","unstructured":"Kovacevic I, Sakaue T, Majolee J, Pronk MC, Maekawa M, Geerts D et al (2018) The Cullin-3-Rbx1-KCTD10 complex controls endothelial barrier function via K63 ubiquitination of RhoB. J Cell Biol 217:1015\u20131032","journal-title":"J Cell Biol"},{"key":"789_CR30","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1046\/j.1471-4159.2002.01078.x","volume":"82","author":"M Kruger","year":"2002","unstructured":"Kruger M, Schafer K, Braun T (2002) The homeobox containing gene Lbx1 is required for correct dorsal-ventral patterning of the neural tube. J Neurochem 82:774\u2013782","journal-title":"J Neurochem"},{"key":"789_CR31","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1056\/NEJMra1705346","volume":"380","author":"AA Levin","year":"2019","unstructured":"Levin AA (2019) Treating disease at the RNA level with oligonucleotides. N Engl J Med 380:57\u201370","journal-title":"N Engl J Med"},{"key":"789_CR32","doi-asserted-by":"publisher","first-page":"3331","DOI":"10.1084\/jem.20171178","volume":"214","author":"MA Lopez-Ramirez","year":"2017","unstructured":"Lopez-Ramirez MA, Fonseca G, Zeineddine HA, Girard R, Moore T, Pham A et al (2017) Thrombospondin1 (TSP1) replacement prevents cerebral cavernous malformations. J Exp Med 214:3331\u20133346","journal-title":"J Exp Med"},{"key":"789_CR33","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1182\/blood-2018-06-856062","volume":"133","author":"MA Lopez-Ramirez","year":"2019","unstructured":"Lopez-Ramirez MA, Pham A, Girard R, Wyseure T, Hale P, Yamashita A et al (2019) Cerebral cavernous malformations form an anticoagulant vascular domain in humans and mice. Blood 133:193\u2013204","journal-title":"Blood"},{"key":"789_CR34","doi-asserted-by":"publisher","first-page":"3737","DOI":"10.1073\/pnas.1012617108","volume":"108","author":"A Louvi","year":"2011","unstructured":"Louvi A, Chen L, Two AM, Zhang H, Min W, Gunel M (2011) Loss of cerebral cavernous malformation 3 (Ccm3) in neuroglia leads to CCM and vascular pathology. Proc Natl Acad Sci U S A 108:3737\u20133742","journal-title":"Proc Natl Acad Sci U S A"},{"key":"789_CR35","doi-asserted-by":"publisher","first-page":"C719","DOI":"10.1152\/ajpcell.2001.280.4.C719","volume":"280","author":"H Lum","year":"2001","unstructured":"Lum H, Roebuck KA (2001) Oxidant stress and endothelial cell dysfunction. Am J Physiol Cell Physiol 280:C719\u2013C741","journal-title":"Am J Physiol Cell Physiol"},{"key":"789_CR36","doi-asserted-by":"crossref","unstructured":"Lyne S, Girard R, Koskim\u00e4ki J, Zeineddine HA, Zhang D, Cao Y et al. (2019) Biomarkers of cavernous Angioma with symptomatic hemorrhage. JCI insight 20;4(12);e128577","DOI":"10.1172\/jci.insight.128577"},{"key":"789_CR37","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1038\/nature12207","volume":"498","author":"L Maddaluno","year":"2013","unstructured":"Maddaluno L, Rudini N, Cuttano R, Bravi L, Giampietro C, Corada M et al (2013) EndMT contributes to the onset and progression of cerebral cavernous malformations. Nature 498:492\u2013496","journal-title":"Nature"},{"key":"789_CR38","doi-asserted-by":"publisher","first-page":"4288","DOI":"10.1093\/nar\/gks042","volume":"40","author":"DJ McCarthy","year":"2012","unstructured":"McCarthy DJ, Chen Y, Smyth GK (2012) Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation. Nucleic Acids Res 40:4288\u20134297","journal-title":"Nucleic Acids Res"},{"key":"789_CR39","doi-asserted-by":"publisher","first-page":"4357","DOI":"10.1093\/hmg\/ddu153","volume":"23","author":"DA McDonald","year":"2014","unstructured":"McDonald DA, Shi C, Shenkar R, Gallione CJ, Akers AL, Li S et al (2014) Lesions from patients with sporadic cerebral cavernous malformations harbor somatic mutations in the CCM genes: evidence for a common biochemical pathway for CCM pathogenesis. Hum Mol Genet 23:4357\u20134370","journal-title":"Hum Mol Genet"},{"key":"789_CR40","doi-asserted-by":"publisher","first-page":"101","DOI":"10.3390\/genes4020101","volume":"4","author":"U Moens","year":"2013","unstructured":"Moens U, Kostenko S, Sveinbjornsson B (2013) The role of mitogen-activated protein kinase-activated protein kinases (MAPKAPKs) in inflammation. Genes (Basel) 4:101\u2013133","journal-title":"Genes (Basel)"},{"key":"789_CR41","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.phrs.2018.10.026","volume":"137","author":"AJ Mouton","year":"2018","unstructured":"Mouton AJ, Rivera Gonzalez OJ, Kaminski AR, Moore ET, Lindsey ML (2018) Matrix metalloproteinase-12 as an endogenous resolution promoting factor following myocardial infarction. Pharmacol Res 137:252\u2013258","journal-title":"Pharmacol Res"},{"key":"789_CR42","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/0959-437X(93)90095-7","volume":"3","author":"M Noll","year":"1993","unstructured":"Noll M (1993) Evolution and role of Pax genes. Curr Opin Genet Dev 3:595\u2013605","journal-title":"Curr Opin Genet Dev"},{"key":"789_CR43","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1002\/jnr.24247","volume":"96","author":"EA Obana","year":"2018","unstructured":"Obana EA, Zhou Q, Furmanski O, Doughty ML (2018) Conditional deletion of Neurog1 in the cerebellum of postnatal mice delays inhibitory interneuron maturation. J Neurosci Res 96:1560\u20131575","journal-title":"J Neurosci Res"},{"key":"789_CR44","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1128\/MCB.24.5.1823-1835.2004","volume":"24","author":"GR Panta","year":"2004","unstructured":"Panta GR, Kaur S, Cavin LG, Cortes ML, Mercurio F, Lothstein L et al (2004) ATM and the catalytic subunit of DNA-dependent protein kinase activate NF-kappaB through a common MEK\/extracellular signal-regulated kinase\/p90(rsk) signaling pathway in response to distinct forms of DNA damage. Mol Cell Biol 24:1823\u20131835","journal-title":"Mol Cell Biol"},{"key":"789_CR45","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1002\/eji.201041303","volume":"42","author":"SA Parsons","year":"2012","unstructured":"Parsons SA, Sharma R, Roccamatisi DL, Zhang H, Petri B, Kubes P et al (2012) Endothelial paxillin and focal adhesion kinase (FAK) play a critical role in neutrophil transmigration. Eur J Immunol 42:436\u2013446","journal-title":"Eur J Immunol"},{"key":"789_CR46","doi-asserted-by":"publisher","first-page":"4721","DOI":"10.1038\/onc.2011.173","volume":"30","author":"J Poschl","year":"2011","unstructured":"Poschl J, Lorenz A, Hartmann W, von Bueren AO, Kool M, Li S et al (2011) Expression of BARHL1 in medulloblastoma is associated with prolonged survival in mice and humans. Oncogene 30:4721\u20134730","journal-title":"Oncogene"},{"key":"789_CR47","doi-asserted-by":"publisher","first-page":"R506","DOI":"10.1016\/j.cub.2007.04.032","volume":"17","author":"M Rape","year":"2007","unstructured":"Rape M (2007) Cell cycle: on-time delivery of Plk1 during cytokinesis. Curr Biol 17:R506\u2013R508","journal-title":"Curr Biol"},{"key":"789_CR48","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.biocel.2016.09.011","volume":"81","author":"SF Retta","year":"2016","unstructured":"Retta SF, Glading AJ (2016) Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: Two sides of the same coin. Int J Biochem Cell Biol 81:254\u2013270","journal-title":"Int J Biochem Cell Biol"},{"key":"789_CR49","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","volume":"26","author":"MD Robinson","year":"2010","unstructured":"Robinson MD, McCarthy DJ, Smyth GK (2010) edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26:139\u2013140","journal-title":"Bioinformatics"},{"key":"789_CR50","doi-asserted-by":"publisher","first-page":"R25","DOI":"10.1186\/gb-2010-11-3-r25","volume":"11","author":"MD Robinson","year":"2010","unstructured":"Robinson MD, Oshlack A (2010) A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol 11:R25","journal-title":"Genome Biol"},{"key":"789_CR51","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1016\/j.arcmed.2005.11.012","volume":"37","author":"A Rojas","year":"2006","unstructured":"Rojas A, Figueroa H, Re L, Morales MA (2006) Oxidative stress at the vascular wall. Mechanistic and pharmacological aspects. Arch Med Res 37:436\u2013448","journal-title":"Arch Med Res"},{"key":"789_CR52","doi-asserted-by":"publisher","first-page":"W467","DOI":"10.1093\/nar\/gkv555","volume":"43","author":"A Rueda","year":"2015","unstructured":"Rueda A, Barturen G, Lebron R, Gomez-Martin C, Alganza A, Oliver JL et al (2015) sRNAtoolbox: an integrated collection of small RNA research tools. Nucleic Acids Res 43:W467\u2013W473","journal-title":"Nucleic Acids Res"},{"key":"789_CR53","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1111\/cas.13133","volume":"108","author":"T Sakaue","year":"2017","unstructured":"Sakaue T, Fujisaki A, Nakayama H, Maekawa M, Hiyoshi H, Kubota E et al (2017) Neddylated Cullin 3 is required for vascular endothelial-cadherin-mediated endothelial barrier function. Cancer Sci 108:208\u2013215","journal-title":"Cancer Sci"},{"key":"789_CR54","doi-asserted-by":"publisher","first-page":"42845","DOI":"10.1038\/srep42845","volume":"7","author":"T Sakaue","year":"2017","unstructured":"Sakaue T, Sakakibara I, Uesugi T, Fujisaki A, Nakashiro KI, Hamakawa H et al (2017) The CUL3-SPOP-DAXX axis is a novel regulator of VEGFR2 expression in vascular endothelial cells. Sci Rep 7:42845","journal-title":"Sci Rep"},{"key":"789_CR55","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1097\/NEN.0b013e31821bc40e","volume":"70","author":"H Schneider","year":"2011","unstructured":"Schneider H, Errede M, Ulrich NH, Virgintino D, Frei K, Bertalanffy H (2011) Impairment of tight junctions and glucose transport in endothelial cells of human cerebral cavernous malformations. J Neuropathol Exp Neurol 70:417\u2013429","journal-title":"J Neuropathol Exp Neurol"},{"issue":"Suppl 1","key":"789_CR56","doi-asserted-by":"publisher","first-page":"i109","DOI":"10.1136\/ard.2010.140533","volume":"70","author":"HB Schonthaler","year":"2011","unstructured":"Schonthaler HB, Guinea-Viniegra J, Wagner EF (2011) Targeting inflammation by modulating the Jun\/AP-1 pathway. Ann Rheum Dis 70(Suppl 1):i109\u2013i112","journal-title":"Ann Rheum Dis"},{"key":"789_CR57","doi-asserted-by":"publisher","first-page":"7758","DOI":"10.1128\/MCB.24.17.7758-7768.2004","volume":"24","author":"WF Schwindinger","year":"2004","unstructured":"Schwindinger WF, Giger KE, Betz KS, Stauffer AM, Sunderlin EM, Sim-Selley LJ et al (2004) Mice with deficiency of G protein gamma3 are lean and have seizures. Mol Cell Biol 24:7758\u20137768","journal-title":"Mol Cell Biol"},{"key":"789_CR58","doi-asserted-by":"publisher","first-page":"7121","DOI":"10.1074\/jbc.M111.308395","volume":"287","author":"WF Schwindinger","year":"2012","unstructured":"Schwindinger WF, Mirshahi UL, Baylor KA, Sheridan KM, Stauffer AM, Usefof S et al (2012) Synergistic roles for G-protein gamma3 and gamma7 subtypes in seizure susceptibility as revealed in double knock-out mice. J Biol Chem 287:7121\u20137133","journal-title":"J Biol Chem"},{"key":"789_CR59","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1161\/STROKEAHA.118.024058","volume":"50","author":"R Shenkar","year":"2019","unstructured":"Shenkar R, Peiper A, Pardo H, Moore T, Lightle R, Girard R et al (2019) Rho kinase inhibition blunts lesion development and hemorrhage in murine models of aggressive Pdcd10\/Ccm3 disease. Stroke 50:738\u2013744","journal-title":"Stroke"},{"key":"789_CR60","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1161\/STROKEAHA.116.015013","volume":"48","author":"R Shenkar","year":"2017","unstructured":"Shenkar R, Shi C, Austin C, Moore T, Lightle R, Cao Y et al (2017) RhoA kinase inhibition with fasudil versus simvastatin in murine models of cerebral cavernous malformations. Stroke 48:187\u2013194","journal-title":"Stroke"},{"key":"789_CR61","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1227\/01.NEU.0000298897.38979.07","volume":"61","author":"R Shenkar","year":"2007","unstructured":"Shenkar R, Shi C, Check IJ, Lipton HL, Awad IA (2007) Concepts and hypotheses: inflammatory hypothesis in the pathogenesis of cerebral cavernous malformations. Neurosurgery 61:693\u2013702 discussion 702-693","journal-title":"Neurosurgery"},{"key":"789_CR62","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1038\/gim.2014.97","volume":"17","author":"R Shenkar","year":"2015","unstructured":"Shenkar R, Shi C, Rebeiz T, Stockton RA, McDonald DA, Mikati AG et al (2015) Exceptional aggressiveness of cerebral cavernous malformation disease associated with PDCD10 mutations. Genet Med 17:188\u2013196","journal-title":"Genet Med"},{"key":"789_CR63","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1007\/s11481-016-9670-0","volume":"11","author":"C Shi","year":"2016","unstructured":"Shi C, Shenkar R, Zeineddine HA, Girard R, Fam MD, Austin C et al (2016) B-cell depletion reduces the maturation of cerebral cavernous malformations in murine models. J NeuroImmune Pharmacol 11:369\u2013377","journal-title":"J NeuroImmune Pharmacol"},{"key":"789_CR64","doi-asserted-by":"publisher","first-page":"57","DOI":"10.4161\/cc.11.1.18775","volume":"11","author":"KT Siu","year":"2012","unstructured":"Siu KT, Rosner MR, Minella AC (2012) An integrated view of cyclin E function and regulation. Cell Cycle 11:57\u201364","journal-title":"Cell Cycle"},{"key":"789_CR65","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/2045-824X-5-6","volume":"5","author":"JM Stiles","year":"2013","unstructured":"Stiles JM, Rowntree RK, Amaya C, Diaz D, Kokta V, Mitchell DC et al (2013) Gene expression analysis reveals marked differences in the transcriptome of infantile hemangioma endothelial cells compared to normal dermal microvascular endothelial cells. Vasc Cell 5:6","journal-title":"Vasc Cell"},{"key":"789_CR66","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1084\/jem.20150519","volume":"213","author":"A Takeuchi","year":"2016","unstructured":"Takeuchi A, Badr Mel S, Miyauchi K, Ishihara C, Onishi R, Guo Z et al (2016) CRTAM determines the CD4+ cytotoxic T lymphocyte lineage. J Exp Med 213:123\u2013138","journal-title":"J Exp Med"},{"key":"789_CR67","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1038\/nature22075","volume":"545","author":"AT Tang","year":"2017","unstructured":"Tang AT, Choi JP, Kotzin JJ, Yang Y, Hong CC, Hobson N et al (2017) Endothelial TLR4 and the microbiome drive cerebral cavernous malformations. Nature 545:305\u2013310","journal-title":"Nature"},{"key":"789_CR68","doi-asserted-by":"publisher","first-page":"503","DOI":"10.3727\/096504016X14755368915591","volume":"25","author":"F Wan","year":"2017","unstructured":"Wan F, Peng L, Zhu C, Zhang X, Chen F, Liu T (2017) Knockdown of latent transforming growth factor-beta (TGF-beta)-binding protein 2 (LTBP2) inhibits invasion and tumorigenesis in thyroid carcinoma cells. Oncol Res 25:503\u2013510","journal-title":"Oncol Res"},{"key":"789_CR69","first-page":"1886","volume":"52","author":"J Wang","year":"2018","unstructured":"Wang J, Liang WJ, Min GT, Wang HP, Chen W, Yao N (2018) LTBP2 promotes the migration and invasion of gastric cancer cells and predicts poor outcome of patients with gastric cancer. Int J Oncol 52:1886\u20131898","journal-title":"Int J Oncol"},{"key":"789_CR70","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1038\/nm.1911","volume":"15","author":"KJ Whitehead","year":"2009","unstructured":"Whitehead KJ, Chan AC, Navankasattusas S, Koh W, London NR, Ling J et al (2009) The cerebral cavernous malformation signaling pathway promotes vascular integrity via rho GTPases. Nat Med 15:177\u2013184","journal-title":"Nat Med"},{"key":"789_CR71","doi-asserted-by":"publisher","first-page":"D146","DOI":"10.1093\/nar\/gku1104","volume":"43","author":"N Wong","year":"2015","unstructured":"Wong N, Wang X (2015) miRDB: an online resource for microRNA target prediction and functional annotations. Nucleic Acids Res 43:D146\u2013D152","journal-title":"Nucleic Acids Res"},{"key":"789_CR72","doi-asserted-by":"publisher","first-page":"12640","DOI":"10.1073\/pnas.1000132107","volume":"107","author":"J Wustehube","year":"2010","unstructured":"Wustehube J, Bartol A, Liebler SS, Brutsch R, Zhu Y, Felbor U et al (2010) Cerebral cavernous malformation protein CCM1 inhibits sprouting angiogenesis by activating DELTA-NOTCH signaling. Proc Natl Acad Sci U S A 107:12640\u201312645","journal-title":"Proc Natl Acad Sci U S A"},{"key":"789_CR73","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/s41374-018-0030-y","volume":"99","author":"HA Zeineddine","year":"2019","unstructured":"Zeineddine HA, Girard R, Saadat L, Shen L, Lightle R, Moore T et al (2019) Phenotypic characterization of murine models of cerebral cavernous malformations. Lab Investig 99:319\u2013330","journal-title":"Lab Investig"},{"key":"789_CR74","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1038\/nm.4169","volume":"22","author":"HJ Zhou","year":"2016","unstructured":"Zhou HJ, Qin L, Zhang H, Tang W, Ji W, He Y et al (2016) Endothelial exocytosis of angiopoietin-2 resulting from CCM3 deficiency contributes to cerebral cavernous malformation. Nat Med 22:1033\u20131042","journal-title":"Nat Med"},{"key":"789_CR75","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1016\/S0891-5849(01)00719-5","volume":"31","author":"LZ Zhou","year":"2001","unstructured":"Zhou LZ, Johnson AP, Rando TA (2001) NF kappa B and AP-1 mediate transcriptional responses to oxidative stress in skeletal muscle cells. Free Radic Biol Med 31:1405\u20131416","journal-title":"Free Radic Biol Med"},{"key":"789_CR76","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1038\/nature17178","volume":"532","author":"Z Zhou","year":"2016","unstructured":"Zhou Z, Tang AT, Wong WY, Bamezai S, Goddard LM, Shenkar R et al (2016) Cerebral cavernous malformations arise from endothelial gain of MEKK3-KLF2\/4 signalling. Nature 532:122\u2013126","journal-title":"Nature"},{"key":"789_CR77","first-page":"702","volume":"8","author":"J Zhu","year":"2015","unstructured":"Zhu J, Chen X, Liao Z, He C, Hu X (2015) TGFBI protein high expression predicts poor prognosis in colorectal cancer patients. Int J Clin Exp Pathol 8:702\u2013710","journal-title":"Int J Clin Exp Pathol"}],"container-title":["Acta Neuropathologica Communications"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-019-0789-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s40478-019-0789-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-019-0789-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,17]],"date-time":"2020-08-17T23:25:28Z","timestamp":1597706728000},"score":1,"resource":{"primary":{"URL":"https:\/\/actaneurocomms.biomedcentral.com\/articles\/10.1186\/s40478-019-0789-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,19]]},"references-count":77,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["789"],"URL":"https:\/\/doi.org\/10.1186\/s40478-019-0789-0","relation":{},"ISSN":["2051-5960"],"issn-type":[{"value":"2051-5960","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,19]]},"assertion":[{"value":"14 June 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 August 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 August 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All mice experiments were performed in compliance with animal procedure protocols and approved by local Institutional Animal Care and Use Committees at the University of Chicago, University of California San Diego, and Duke University.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"132"}}