{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:14:44Z","timestamp":1792782884768,"version":"4.5.0"},"reference-count":79,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"European Union\u2019s Horizon 2020 research and innovation program under the Marie Sk\u0142odowska-Curie grant agreement","award":["814316"],"award-info":[{"award-number":["814316"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program under the Marie Sk\u0142odowska-Curie grant agreement","award":["814316"],"award-info":[{"award-number":["814316"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program under the Marie Sk\u0142odowska-Curie grant agreement","award":["814316"],"award-info":[{"award-number":["814316"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program under the Marie Sk\u0142odowska-Curie grant agreement","award":["814316"],"award-info":[{"award-number":["814316"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program under the Marie Sk\u0142odowska-Curie grant agreement","award":["814316"],"award-info":[{"award-number":["814316"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program under the Marie Sk\u0142odowska-Curie grant agreement","award":["814316"],"award-info":[{"award-number":["814316"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program under the Marie Sk\u0142odowska-Curie grant agreement","award":["814316"],"award-info":[{"award-number":["814316"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Angiogenesis"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Induced pluripotent stem cell (iPSC) derived endothelial cells (iECs) have emerged as a promising tool for studying vascular biology and providing a platform for modelling various vascular diseases, including those with genetic origins. Currently, primary ECs are the main source for disease modelling in this field. However, they are difficult to edit and have a limited lifespan. To study the effects of targeted mutations on an endogenous level, we generated and characterized an iPSC derived model for venous malformations (VMs). CRISPR-Cas9 technology was used to generate a novel human iPSC line with an amino acid substitution L914F in the TIE2 receptor, known to cause VMs. This enabled us to study the differential effects of VM causative mutations in iECs in multiple in vitro models and assess their ability to form vessels in vivo. The analysis of TIE2 expression levels in TIE2\n                    <jats:sup>L914F<\/jats:sup>\n                    iECs showed a significantly lower expression of TIE2 on mRNA and protein level, which has not been observed before due to a lack of models with endogenous edited TIE2\n                    <jats:sup>L914F<\/jats:sup>\n                    and sparse patient data. Interestingly, the TIE2 pathway was still significantly upregulated and TIE2 showed high levels of phosphorylation. TIE2\n                    <jats:sup>L914F<\/jats:sup>\n                    iECs exhibited dysregulated angiogenesis markers and upregulated migration capability, while proliferation was not affected. Under shear stress TIE2\n                    <jats:sup>L914F<\/jats:sup>\n                    iECs showed reduced alignment in the flow direction and a larger cell area than TIE2\n                    <jats:sup>WT<\/jats:sup>\n                    iECs. In summary, we developed a novel TIE2\n                    <jats:sup>L914F<\/jats:sup>\n                    iPSC-derived iEC model and characterized it in multiple in vitro models. The model can be used in future work for drug screening for novel treatments for VMs.\n                  <\/jats:p>","DOI":"10.1007\/s10456-024-09925-9","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T07:01:59Z","timestamp":1716274919000},"page":"523-542","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Human iPSC and CRISPR targeted gene knock-in strategy for studying the somatic TIE2L914F mutation in endothelial cells"],"prefix":"10.1007","volume":"27","author":[{"given":"Bojana","family":"Lazovic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoang-Tuan","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammadhassan","family":"Ansarizadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leif","family":"Wigge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Kohl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songyuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Carracedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jere","family":"Kettunen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Krimpenfort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramy","family":"Elgendy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kati","family":"Richter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laknee","family":"De Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilada","family":"Bilican","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prateek","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pratik","family":"Saxena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Jakobsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuechong","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauri","family":"Eklund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Hicks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,21]]},"reference":[{"key":"9925_CR1","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1161\/CIRCRESAHA.117.306290","volume":"117","author":"P Abrahimi","year":"2015","unstructured":"Abrahimi P, Chang WG, Kluger MS et al (2015) Efficient gene disruption in cultured primary human endothelial cells by CRISPR\/Cas9. Circ Res 117:121\u2013128. https:\/\/doi.org\/10.1161\/CIRCRESAHA.117.306290","journal-title":"Circ Res"},{"key":"9925_CR2","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1111\/bcpt.13027","volume":"123","author":"J Kangas","year":"2018","unstructured":"Kangas J, N\u00e4tynki M, Eklund L (2018) Development of molecular therapies for venous malformations. Basic Clin Pharmacol Toxicol 123:6\u201319. https:\/\/doi.org\/10.1111\/bcpt.13027","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"9925_CR3","doi-asserted-by":"publisher","first-page":"256","DOI":"10.5483\/BMBRep.2015.48.5.100","volume":"48","author":"C Kim","year":"2015","unstructured":"Kim C (2015) iPSC technology-Powerful hand for disease modeling and therapeutic screen. BMB Rep 48:256\u2013265. https:\/\/doi.org\/10.5483\/BMBRep.2015.48.5.100","journal-title":"BMB Rep"},{"key":"9925_CR4","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","volume":"126","author":"K Takahashi","year":"2006","unstructured":"Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663\u2013676. https:\/\/doi.org\/10.1016\/j.cell.2006.07.024","journal-title":"Cell"},{"key":"9925_CR5","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","volume":"131","author":"K Takahashi","year":"2007","unstructured":"Takahashi K, Tanabe K, Ohnuki M et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861\u2013872. https:\/\/doi.org\/10.1016\/j.cell.2007.11.019","journal-title":"Cell"},{"key":"9925_CR6","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/nrd.2016.245","volume":"16","author":"Y Shi","year":"2017","unstructured":"Shi Y, Inoue H, Wu JC, Yamanaka S (2017) Induced pluripotent stem cell technology: a decade of progress. Nat Rev Drug Discov 16:115\u2013130. https:\/\/doi.org\/10.1038\/nrd.2016.245","journal-title":"Nat Rev Drug Discov"},{"key":"9925_CR7","doi-asserted-by":"publisher","first-page":"3058","DOI":"10.1073\/pnas.94.7.3058","volume":"94","author":"TM Schlaeger","year":"1997","unstructured":"Schlaeger TM, Bartunkova S, Lawitts JA et al (1997) Uniform vascular-endothelial-cell-specific gene expression in both embryonic and adult transgenic mice (transcriptionenhancer). Cell Biology 94:3058\u20133063. https:\/\/doi.org\/10.1073\/pnas.94.7.3058","journal-title":"Cell Biology"},{"key":"9925_CR8","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1242\/dev.119.3.957","volume":"119","author":"H Schn\u00fcrch","year":"1993","unstructured":"Schn\u00fcrch H, Risau W (1993) Expression of TIE-2, a member of a novel family of receptor tyrosine kinases, in the endothelial cell lineage. Development 119:957\u2013968. https:\/\/doi.org\/10.1242\/dev.119.3.957","journal-title":"Development"},{"key":"9925_CR9","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1101\/gad.8.16.1897","volume":"8","author":"DJ Dumont","year":"1994","unstructured":"Dumont DJ, Gradwohl G, Fong G-H et al (1994) Dominant-negative and targeted null mutations in the endothelial receptor tyrosine kinase, TEK, reveal a critical role in vasculogenesis of the embryo. Genes Dev 8:1897\u20131909. https:\/\/doi.org\/10.1101\/gad.8.16.1897","journal-title":"Genes Dev"},{"key":"9925_CR10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1006\/mvre.1998.2081","volume":"56","author":"S Patan","year":"1998","unstructured":"Patan S (1998) TIE1 and TIE2 receptor tyrosine kinases inversely regulate embryonic angiogenesis by the mechanism of intussusceptive microvascular growth. Microvasc Res 56:1\u201321. https:\/\/doi.org\/10.1006\/mvre.1998.2081","journal-title":"Microvasc Res"},{"key":"9925_CR11","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1038\/376070a0","volume":"376","author":"TN Sato","year":"1995","unstructured":"Sato TN, Tozawa Y, Deutsch U et al (1995) Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation. Nature 376:70\u201374. https:\/\/doi.org\/10.1038\/376070a0","journal-title":"Nature"},{"key":"9925_CR12","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/S1074-7613(00)80665-2","volume":"9","author":"N Takakura","year":"1998","unstructured":"Takakura N, Huang XL, Naruse T et al (1998) Critical role of the TIE2 endothelial cell receptor in the development of definitive hematopoiesis. Immunity 9:677\u2013686. https:\/\/doi.org\/10.1016\/S1074-7613(00)80665-2","journal-title":"Immunity"},{"key":"9925_CR13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fnmol.2011.00051","volume":"4","author":"J Karar","year":"2011","unstructured":"Karar J, Maity A (2011) PI3K\/AKT\/mTOR pathway in angiogenesis. Front Mol Neurosci 4:1\u20138. https:\/\/doi.org\/10.3389\/fnmol.2011.00051","journal-title":"Front Mol Neurosci"},{"key":"9925_CR14","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1074\/jbc.M208550200","volume":"278","author":"U Fiedler","year":"2003","unstructured":"Fiedler U, Krissl T, Koidl S et al (2003) Angiopoietin-1 and angiopoietin-2 share the same binding domains in the Tie-2 receptor involving the first Ig-like loop and the epidermal growth factor-like repeats. J Biol Chem 278:1721\u20131727. https:\/\/doi.org\/10.1074\/jbc.M208550200","journal-title":"J Biol Chem"},{"key":"9925_CR15","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1038\/sj.onc.1202115","volume":"17","author":"N Jones","year":"1998","unstructured":"Jones N, Dumont DJ (1998) The Tek\/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R. Oncogene 17:1097\u20131108. https:\/\/doi.org\/10.1038\/sj.onc.1202115","journal-title":"Oncogene"},{"key":"9925_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.7554\/eLife.37776","volume":"7","author":"H Elamaa","year":"2018","unstructured":"Elamaa H, Kihlstr\u00f6m M, Kapiainen E et al (2018) Angiopoietin-4-dependent venous maturation and fluid drainage in the peripheral retina. Elife 7:1\u201332. https:\/\/doi.org\/10.7554\/eLife.37776","journal-title":"Elife"},{"key":"9925_CR17","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1038\/nrd.2016.278","volume":"16","author":"P Saharinen","year":"2017","unstructured":"Saharinen P, Eklund L, Alitalo K (2017) Therapeutic targeting of the angiopoietin-TIE pathway. Nat Rev Drug Discov 16:635\u2013661. https:\/\/doi.org\/10.1038\/nrd.2016.278","journal-title":"Nat Rev Drug Discov"},{"key":"9925_CR18","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1073\/pnas.96.5.1904","volume":"96","author":"DM Valenzuela","year":"1999","unstructured":"Valenzuela DM, Griffiths JA, Rojas J et al (1999) Angiopoietins 3 and 4: diverging gene counterparts in mice and humans. Biochem Commun P R Vagelos 96:194\u2013199. https:\/\/doi.org\/10.1073\/pnas.96.5.1904","journal-title":"Biochem Commun P R Vagelos"},{"key":"9925_CR19","doi-asserted-by":"publisher","first-page":"4376","DOI":"10.1073\/pnas.1616166114","volume":"114","author":"VM Lepp\u00e4nen","year":"2017","unstructured":"Lepp\u00e4nen VM, Saharinen P, Alitalo K (2017) Structural basis of Tie2 activation and Tie2\/Tie1 heterodimerization. Proc Natl Acad Sci U S A 114:4376\u20134381. https:\/\/doi.org\/10.1073\/pnas.1616166114","journal-title":"Proc Natl Acad Sci U S A"},{"key":"9925_CR20","doi-asserted-by":"publisher","first-page":"6287","DOI":"10.1038\/s41467-021-26620-1","volume":"12","author":"G Jo","year":"2021","unstructured":"Jo G, Bae J, Hong HJ et al (2021) Structural insights into the clustering and activation of Tie2 receptor mediated by Tie2 agonistic antibody. Nat Commun 12:6287. https:\/\/doi.org\/10.1038\/s41467-021-26620-1","journal-title":"Nat Commun"},{"key":"9925_CR21","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1038\/ncb1714","volume":"10","author":"S Fukuhara","year":"2008","unstructured":"Fukuhara S, Sako K, Minami T et al (2008) Differential function of Tie2 at cell-cell contacts and cell-substratum contacts regulated by angiopoietin-1. Nat Cell Biol 10:513\u2013526. https:\/\/doi.org\/10.1038\/ncb1714","journal-title":"Nat Cell Biol"},{"key":"9925_CR22","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1038\/ncb1715","volume":"10","author":"P Saharinen","year":"2008","unstructured":"Saharinen P, Eklund L, Miettinen J et al (2008) Angiopoietins assemble distinct Tie2 signalling complexes in endothelial cell-cell and cell-matrix contacts. Nat Cell Biol 10:527\u2013537. https:\/\/doi.org\/10.1038\/ncb1715","journal-title":"Nat Cell Biol"},{"key":"9925_CR23","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.1128\/mcb.01472-08","volume":"29","author":"HT Yuan","year":"2009","unstructured":"Yuan HT, Khankin EV, Karumanchi SA, Parikh SM (2009) Angiopoietin 2 Is a partial agonist\/antagonist of Tie2 signaling in the endothelium. Mol Cell Biol 29:2011\u20132022. https:\/\/doi.org\/10.1128\/mcb.01472-08","journal-title":"Mol Cell Biol"},{"key":"9925_CR24","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1126\/science.277.5322.55","volume":"277","author":"PC Maisonpierre","year":"1997","unstructured":"Maisonpierre PC, Suri C, Jones PF et al (1997) Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science (1979) 277:55\u201360. https:\/\/doi.org\/10.1126\/science.277.5322.55","journal-title":"Science (1979)"},{"key":"9925_CR25","first-page":"2097","volume":"11","author":"L Huang","year":"1995","unstructured":"Huang L, TCRP& PK (1995) GRB2 and SH-PTP2: potentially important endothelial signaling molecules downstream of the TEK\/TIE2 receptor tyrosine kinase. Oncogene 11:2097\u20132103","journal-title":"Oncogene"},{"key":"9925_CR26","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1161\/01.RES.86.1.24","volume":"86","author":"I Kim","year":"2000","unstructured":"Kim I, Kim HG, So JN et al (2000) Angiopoietin-1 regulates endothelial cell survival through the phosphatidylinositol 3\u2019-kinase\/Akt signal transduction pathway. Circ Res 86:24\u201329. https:\/\/doi.org\/10.1161\/01.RES.86.1.24","journal-title":"Circ Res"},{"key":"9925_CR27","doi-asserted-by":"publisher","first-page":"4131","DOI":"10.1128\/MCB.18.7.4131","volume":"18","author":"CD Kontos","year":"1998","unstructured":"Kontos CD, Stauffer TP, Yang W-P et al (1998) Tyrosine 1101 of Tie2 is the major site of association of p85 and is required for activation of phosphatidylinositol 3-kinase and Akt. Mol Cell Biol 18:4131\u20134140. https:\/\/doi.org\/10.1128\/MCB.18.7.4131","journal-title":"Mol Cell Biol"},{"key":"9925_CR28","doi-asserted-by":"publisher","first-page":"30896","DOI":"10.1074\/jbc.274.43.30896","volume":"274","author":"N Jones","year":"1999","unstructured":"Jones N, Master Z, Jones J et al (1999) Identification of Tek\/Tie2 binding partners. Binding to a multifunctional docking site mediates cell survival and migration. J Biol Chem 274:30896\u201330905. https:\/\/doi.org\/10.1074\/jbc.274.43.30896","journal-title":"J Biol Chem"},{"key":"9925_CR29","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.ccc.2019.12.003","volume":"36","author":"KD Sack","year":"2020","unstructured":"Sack KD, Kellum JA, Parikh SM (2020) The angiopoietin-Tie2 pathway in critical illness. Crit Care Clin 36:201\u2013216. https:\/\/doi.org\/10.1016\/j.ccc.2019.12.003","journal-title":"Crit Care Clin"},{"key":"9925_CR30","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1038\/ng.272.Somatic","volume":"41","author":"N Limaye","year":"2009","unstructured":"Limaye N, Wouters V, Uebelhoer M et al (2009) Somatic Mutations in the angiopoietin-receptor TIE2 can cause both solitary and multiple sporadic venous malformations. Nat Genet 41:118\u2013124. https:\/\/doi.org\/10.1038\/ng.272.Somatic","journal-title":"Nat Genet"},{"key":"9925_CR31","doi-asserted-by":"publisher","first-page":"3438","DOI":"10.1093\/hmg\/ddt198","volume":"22","author":"M Uebelhoer","year":"2013","unstructured":"Uebelhoer M, N\u00e4tynki M, Kangas J et al (2013) Venous malformation-causative TIE2 mutations mediate an AKT-dependent decrease in PDGFB. Hum Mol Genet 22:3438\u20133448. https:\/\/doi.org\/10.1093\/hmg\/ddt198","journal-title":"Hum Mol Genet"},{"key":"9925_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-019-48854-2","volume":"9","author":"Y Cai","year":"2019","unstructured":"Cai Y, Schrenk S, Goines J et al (2019) Constitutive active mutant TIE2 induces enlarged vascular lumen formation with loss of apico-basal polarity and pericyte recruitment. Sci Rep 9:1\u201312. https:\/\/doi.org\/10.1038\/s41598-019-48854-2","journal-title":"Sci Rep"},{"key":"9925_CR33","doi-asserted-by":"publisher","first-page":"4903","DOI":"10.1038\/s41467-020-18548-9","volume":"11","author":"A Lundin","year":"2020","unstructured":"Lundin A, Porritt MJ, Jaiswal H et al (2020) Development of an ObLiGaRe doxycycline inducible Cas9 system for pre-clinical cancer drug discovery. Nat Commun 11:4903. https:\/\/doi.org\/10.1038\/s41467-020-18548-9","journal-title":"Nat Commun"},{"key":"9925_CR34","doi-asserted-by":"publisher","first-page":"2832","DOI":"10.1038\/s41467-020-20810-z","volume":"12","author":"S Li","year":"2021","unstructured":"Li S, Akrap N, Cerboni S et al (2021) Universal toxin-based selection for precise genome engineering in human cells. Nat Commun 12:2832. https:\/\/doi.org\/10.1038\/s41467-020-20810-z","journal-title":"Nat Commun"},{"key":"9925_CR35","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1101\/2022.05.17.492193","volume":"6","author":"A Panda","year":"2023","unstructured":"Panda A, Suvakov M, Mariani J et al (2023) Clonally selected lines after CRISPR\/Cas editing are not isogenic. CRISPR J 6:176\u2013182. https:\/\/doi.org\/10.1101\/2022.05.17.492193","journal-title":"CRISPR J"},{"key":"9925_CR36","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1126\/sciadv.aba7606","volume":"24","author":"K Wang","year":"2020","unstructured":"Wang K, Lin RZ, Hong X et al (2020) Robust differentiation of human pluripotent stem cells into endothelial cells via temporal modulation of ETV2 with modified mRNA. Sci Adv 24:6\u201330. https:\/\/doi.org\/10.1126\/sciadv.aba7606","journal-title":"Sci Adv"},{"key":"9925_CR37","doi-asserted-by":"publisher","first-page":"3491","DOI":"10.1172\/JCI76004","volume":"125","author":"E Boscolo","year":"2015","unstructured":"Boscolo E, Limaye N, Huang L et al (2015) Rapamycin improves TIE2-mutated venous malformation in murine model and human subjects. J Clin Investig 125:3491\u20133504. https:\/\/doi.org\/10.1172\/JCI76004","journal-title":"J Clin Investig"},{"key":"9925_CR38","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1016\/j.ajhg.2015.11.011","volume":"97","author":"N Limaye","year":"2015","unstructured":"Limaye N, Kangas J, Mendola A et al (2015) Somatic activating PIK3CA mutations cause venous malformation. Am J Hum Genet 97:914\u2013921. https:\/\/doi.org\/10.1016\/j.ajhg.2015.11.011","journal-title":"Am J Hum Genet"},{"key":"9925_CR39","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.jid.2016.07.034","volume":"137","author":"J Soblet","year":"2017","unstructured":"Soblet J, Kangas J, N\u00e4tynki M et al (2017) Blue Rubber Bleb Nevus (BRBN) syndrome is caused by somatic TEK (TIE2) mutations. J Investig Dermatol 137:207\u2013216. https:\/\/doi.org\/10.1016\/j.jid.2016.07.034","journal-title":"J Investig Dermatol"},{"key":"9925_CR40","doi-asserted-by":"publisher","first-page":"6374","DOI":"10.1093\/hmg\/ddv349","volume":"24","author":"M N\u00e4tynki","year":"2015","unstructured":"N\u00e4tynki M, Kangas J, Miinalainen I et al (2015) Common and specific effects of TIE2 mutations causing venous malformations. Hum Mol Genet 24:6374\u20136389. https:\/\/doi.org\/10.1093\/hmg\/ddv349","journal-title":"Hum Mol Genet"},{"key":"9925_CR41","doi-asserted-by":"publisher","first-page":"D447","DOI":"10.1093\/nar\/gku1003","volume":"43","author":"D Szklarczyk","year":"2015","unstructured":"Szklarczyk D, Franceschini A, Wyder S et al (2015) STRING v10: Protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res 43:D447\u2013D452. https:\/\/doi.org\/10.1093\/nar\/gku1003","journal-title":"Nucleic Acids Res"},{"key":"9925_CR42","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.109161","author":"Y Miyamura","year":"2024","unstructured":"Miyamura Y, Kamei S, Matsuo M et al (2024) FOXO1 stimulates tip cell-enriched gene expression in endothelial cells. iScience. https:\/\/doi.org\/10.1016\/j.isci.2024.109161","journal-title":"iScience"},{"key":"9925_CR43","doi-asserted-by":"publisher","first-page":"2382","DOI":"10.1172\/JCI23126","volume":"115","author":"M Potente","year":"2005","unstructured":"Potente M, Urbich C, Sasaki KI et al (2005) Involvement of Foxo transcription factors in angiogenesis and postnatal neovascularization. J Clin Investig 115:2382\u20132392. https:\/\/doi.org\/10.1172\/JCI23126","journal-title":"J Clin Investig"},{"key":"9925_CR44","doi-asserted-by":"crossref","unstructured":"Brunet A, Bonni A, Zigmond MJ, et al (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor","DOI":"10.1016\/S0092-8674(00)80595-4"},{"key":"9925_CR45","doi-asserted-by":"crossref","unstructured":"Safran M, Rosen N, Twik M, et al (2022) The GeneCards Suite. In: Practical guide to life science databases. Springer Nature, pp 27\u201356","DOI":"10.1007\/978-981-16-5812-9_2"},{"key":"9925_CR46","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1093\/bioinformatics\/bts676","volume":"29","author":"F Belinky","year":"2013","unstructured":"Belinky F, Bahir I, Stelzer G et al (2013) Non-redundant compendium of human ncRNA genes in GeneCards. Bioinformatics 29:255\u2013261. https:\/\/doi.org\/10.1093\/bioinformatics\/bts676","journal-title":"Bioinformatics"},{"key":"9925_CR47","doi-asserted-by":"publisher","first-page":"2278","DOI":"10.1172\/JCI46322","volume":"121","author":"M Jeansson","year":"2011","unstructured":"Jeansson M, Gawlik A, Anderson G et al (2011) Angiopoietin-1 is essential in mouse vasculature during development and in response to injury. J Clin Investig 121:2278\u20132289. https:\/\/doi.org\/10.1172\/JCI46322","journal-title":"J Clin Investig"},{"key":"9925_CR48","doi-asserted-by":"publisher","first-page":"2455","DOI":"10.1016\/j.celrep.2018.04.080","volume":"23","author":"KH Kim","year":"2018","unstructured":"Kim KH, Nakaoka Y, Augustin HG, Koh GY (2018) Myocardial angiopoietin-1 controls atrial chamber morphogenesis by spatiotemporal degradation of cardiac jelly. Cell Rep 23:2455\u20132466. https:\/\/doi.org\/10.1016\/j.celrep.2018.04.080","journal-title":"Cell Rep"},{"key":"9925_CR49","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1227\/01.NEU.0000114512.59624.A5","volume":"54","author":"O Guzeloglu-Kayisli","year":"2004","unstructured":"Guzeloglu-Kayisli O, Amankulor NM, Voorhees J et al (2004) KRIT1\/cerebral cavernous malformation 1 protein localizes to vascular endothelium, astrocytes, and pyramidal cells of the adult human cerebral cortex. Neurosurgery 54:943\u2013949. https:\/\/doi.org\/10.1227\/01.NEU.0000114512.59624.A5","journal-title":"Neurosurgery"},{"key":"9925_CR50","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1161\/ATVBAHA.113.302785","volume":"34","author":"JD Kim","year":"2014","unstructured":"Kim JD, Kang Y, Kim J et al (2014) Essential role of apelin signaling during lymphatic development in Zebrafish. Arterioscler Thromb Vasc Biol 34:338\u2013345. https:\/\/doi.org\/10.1161\/ATVBAHA.113.302785","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"9925_CR51","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1007\/s10456-016-9538-1","volume":"20","author":"JA Couto","year":"2017","unstructured":"Couto JA, Ayturk UM, Konczyk DJ et al (2017) A somatic GNA11 mutation is associated with extremity capillary malformation and overgrowth. Angiogenesis 20:303\u2013306. https:\/\/doi.org\/10.1007\/s10456-016-9538-1","journal-title":"Angiogenesis"},{"key":"9925_CR52","doi-asserted-by":"publisher","first-page":"542","DOI":"10.6515\/ACS.202207_38(4).20220210A","volume":"38","author":"MM Chuang","year":"2022","unstructured":"Chuang MM, Wu SH, Charng MJ, Wu YJ (2022) A novel BMPR2 variant gene in relation with hereditary pulmonary arterial hypertension combined with pulmonary arteriovenous malformations. Acta Cardiol Sin 38:542\u2013545. https:\/\/doi.org\/10.6515\/ACS.202207_38(4).20220210A","journal-title":"Acta Cardiol Sin"},{"key":"9925_CR53","doi-asserted-by":"publisher","first-page":"7092","DOI":"10.1021\/acs.nanolett.3c01945","volume":"23","author":"K Cullion","year":"2023","unstructured":"Cullion K, Ostertag-Hill CA, Pan M et al (2023) Ablation of venous malformations by photothermal therapy with intravenous gold nanoshells. Nano Lett 23:7092\u20137099. https:\/\/doi.org\/10.1021\/acs.nanolett.3c01945","journal-title":"Nano Lett"},{"key":"9925_CR54","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1126\/science.1231143","volume":"339","author":"L Cong","year":"1979","unstructured":"Cong L, Ran FA, Cox D et al (1979) (2013) Multiplex genome engineering using CRISPR\/Cas systems. Science 339:819\u2013823. https:\/\/doi.org\/10.1126\/science.1231143","journal-title":"Science"},{"key":"9925_CR55","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/nature09805","volume":"471","author":"A Gore","year":"2011","unstructured":"Gore A, Li Z, Fung HL et al (2011) Somatic coding mutations in human induced pluripotent stem cells. Nature 471:63\u201367. https:\/\/doi.org\/10.1038\/nature09805","journal-title":"Nature"},{"key":"9925_CR56","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1002\/stem.2797","volume":"36","author":"S Assou","year":"2018","unstructured":"Assou S, Bouckenheimer J, De Vos J (2018) Concise review: Assessing the genome integrity of human induced pluripotent stem cells: What quality control metrics? Stem Cells 36:814\u2013821. https:\/\/doi.org\/10.1002\/stem.2797","journal-title":"Stem Cells"},{"key":"9925_CR57","doi-asserted-by":"publisher","unstructured":"Chu M, Li T, Shen B, et al (2016) Angiopoietin receptor Tie2 is required for vein specification and maintenance via regulating COUP-TFII. https:\/\/doi.org\/10.7554\/eLife.21032.001","DOI":"10.7554\/eLife.21032.001"},{"key":"9925_CR58","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2024.02.004","author":"K Hirose","year":"2024","unstructured":"Hirose K, Hori Y, Ozeki M et al (2024) Comprehensive phenotypic and genomic characterization of venous malformations. Hum Pathol. https:\/\/doi.org\/10.1016\/j.humpath.2024.02.004","journal-title":"Hum Pathol"},{"key":"9925_CR59","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1007\/s00441-022-03657-2","volume":"389","author":"GH Chen","year":"2022","unstructured":"Chen GH, Yang JG, Xia HF et al (2022) Endothelial cells induce degradation of ECM through enhanced secretion of MMP14 carried on extracellular vesicles in venous malformation. Cell Tissue Res 389:517\u2013530. https:\/\/doi.org\/10.1007\/s00441-022-03657-2","journal-title":"Cell Tissue Res"},{"key":"9925_CR60","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1039\/c7ib00023e","volume":"9","author":"JG DeStefano","year":"2017","unstructured":"DeStefano JG, Williams A, Wnorowski A et al (2017) Real-time quantification of endothelial response to shear stress and vascular modulators. Integr Biol (United Kingdom) 9:362\u2013374. https:\/\/doi.org\/10.1039\/c7ib00023e","journal-title":"Integr Biol (United Kingdom)"},{"key":"9925_CR61","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-40417-9","author":"S Rosa","year":"2019","unstructured":"Rosa S, Pra\u00e7a C, Pitrez PR et al (2019) Functional characterization of ipsC-derived arterial- and venous-like endothelial cells. Sci Rep. https:\/\/doi.org\/10.1038\/s41598-019-40417-9","journal-title":"Sci Rep"},{"key":"9925_CR62","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1038\/nature24644","volume":"551","author":"NM Gaudelli","year":"2017","unstructured":"Gaudelli NM, Komor AC, Rees HA et al (2017) Programmable base editing of T to G C in genomic DNA without DNA cleavage. Nature 551:464\u2013471. https:\/\/doi.org\/10.1038\/nature24644","journal-title":"Nature"},{"key":"9925_CR63","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","volume":"9","author":"J Schindelin","year":"2012","unstructured":"Schindelin J, Arganda-Carreras I, Frise E et al (2012) Fiji: An open-source platform for biological-image analysis. Nat Methods 9:676\u2013682. https:\/\/doi.org\/10.1038\/nmeth.2019","journal-title":"Nat Methods"},{"key":"9925_CR64","unstructured":"Andrews S, Krueger F, Seconds-Pichon A, et al (2015) FastQC. A quality control tool for high throughput sequence data. Babraham bioinformatics. Babraham Institute"},{"key":"9925_CR65","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1093\/bioinformatics\/btv566","volume":"32","author":"K Okonechnikov","year":"2016","unstructured":"Okonechnikov K, Conesa A, Garc\u00eda-Alcalde F (2016) Qualimap 2: advanced multi-sample quality control for high-throughput sequencing data. Bioinformatics 32:292\u2013294. https:\/\/doi.org\/10.1093\/bioinformatics\/btv566","journal-title":"Bioinformatics"},{"key":"9925_CR66","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","volume":"25","author":"H Li","year":"2009","unstructured":"Li H, Handsaker B, Wysoker A et al (2009) The Sequence Alignment\/Map format and SAMtools. Bioinformatics 25:2078\u20132079. https:\/\/doi.org\/10.1093\/bioinformatics\/btp352","journal-title":"Bioinformatics"},{"key":"9925_CR67","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin A, Davis CA, Schlesinger F et al (2013) STAR: Ultrafast universal RNA-seq aligner. Bioinformatics 29:15\u201321. https:\/\/doi.org\/10.1093\/bioinformatics\/bts635","journal-title":"Bioinformatics"},{"key":"9925_CR68","doi-asserted-by":"publisher","first-page":"3047","DOI":"10.1093\/bioinformatics\/btw354","volume":"32","author":"P Ewels","year":"2016","unstructured":"Ewels P, Magnusson M, Lundin S, K\u00e4ller M (2016) MultiQC: summarize analysis results for multiple tools and samples in a single report. Bioinformatics 32:3047\u20133048. https:\/\/doi.org\/10.1093\/bioinformatics\/btw354","journal-title":"Bioinformatics"},{"key":"9925_CR69","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1186\/s12859-018-2579-2","volume":"19","author":"JM Gaspar","year":"2018","unstructured":"Gaspar JM (2018) NGmerge: Merging paired-end reads via novel empirically-derived models of sequencing errors. BMC Bioinform 19:536. https:\/\/doi.org\/10.1186\/s12859-018-2579-2","journal-title":"BMC Bioinform"},{"key":"9925_CR70","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/nmeth.4197","volume":"14","author":"R Patro","year":"2017","unstructured":"Patro R, Duggal G, Love MI et al (2017) Salmon provides fast and bias-aware quantification of transcript expression. Nat Methods 14:417\u2013419. https:\/\/doi.org\/10.1038\/nmeth.4197","journal-title":"Nat Methods"},{"key":"9925_CR71","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1038\/nbt.3820","volume":"35","author":"P DI Tommaso","year":"2017","unstructured":"DI Tommaso P, Chatzou M, Floden EW et al (2017) Nextflow enables reproducible computational workflows. Nat Biotechnol 35:316\u2013319. https:\/\/doi.org\/10.1038\/nbt.3820","journal-title":"Nat Biotechnol"},{"key":"9925_CR72","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1038\/s41592-018-0046-7","volume":"15","author":"R Dale","year":"2018","unstructured":"Dale R, Gr\u00fcning B, Sj\u00f6din A et al (2018) Bioconda: sustainable and comprehensive software distribution for the life sciences. Nat Methods 15:475\u2013476. https:\/\/doi.org\/10.1038\/s41592-018-0046-7","journal-title":"Nat Methods"},{"key":"9925_CR73","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","volume":"26","author":"MD Robinson","year":"2009","unstructured":"Robinson MD, McCarthy DJ, Smyth GK (2009) edgeR: a bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26:139\u2013140. https:\/\/doi.org\/10.1093\/bioinformatics\/btp616","journal-title":"Bioinformatics"},{"key":"9925_CR74","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie ME, Phipson B, Wu D et al (2015) Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 43:47. https:\/\/doi.org\/10.1093\/nar\/gkv007","journal-title":"Nucleic Acids Res"},{"key":"9925_CR75","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1093\/bioinformatics\/btaa687","volume":"37","author":"GE Hoffman","year":"2021","unstructured":"Hoffman GE, Roussos P (2021) Dream: powerful differential expression analysis for repeated measures designs. Bioinformatics 37:192\u2013201. https:\/\/doi.org\/10.1093\/bioinformatics\/btaa687","journal-title":"Bioinformatics"},{"key":"9925_CR76","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031","volume":"57","author":"Y Benjamini","year":"1995","unstructured":"Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate\u2014a practical and powerful approach to multiple testing. J R Stat Soc Ser B (Methological) 57:289\u2013300. https:\/\/doi.org\/10.1111\/j.2517-6161.1995.tb02031","journal-title":"J R Stat Soc Ser B (Methological)"},{"key":"9925_CR77","doi-asserted-by":"publisher","first-page":"100141","DOI":"10.1016\/j.xinn.2021.100141","volume":"2","author":"T Wu","year":"2021","unstructured":"Wu T, Hu E, Xu S et al (2021) clusterProfiler 4.0: a universal enrichment tool for interpreting omics data. Innovation 2:100141. https:\/\/doi.org\/10.1016\/j.xinn.2021.100141","journal-title":"Innovation"},{"key":"9925_CR78","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1007\/978-1-4939-3578-9_16","volume":"1418","author":"F Hahne","year":"2016","unstructured":"Hahne F, Ivanek R (2016) Visualizing genomic data using Gviz and bioconductor BT\u2014statistical genomics: methods and protocols. Methods Mol Biol 1418:335\u2013351. https:\/\/doi.org\/10.1007\/978-1-4939-3578-9_16","journal-title":"Methods Mol Biol"},{"key":"9925_CR79","doi-asserted-by":"publisher","first-page":"1634","DOI":"10.1038\/s41592-022-01663-4","volume":"19","author":"M Pachitariu","year":"2022","unstructured":"Pachitariu M, Stringer C (2022) Cellpose 2.0: how to train your own model. Nat Methods 19:1634\u20131641. https:\/\/doi.org\/10.1038\/s41592-022-01663-4","journal-title":"Nat Methods"}],"updated-by":[{"DOI":"10.1007\/s10456-024-09932-w","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T00:00:00Z","timestamp":1719360000000}}],"container-title":["Angiogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10456-024-09925-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10456-024-09925-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10456-024-09925-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T11:10:19Z","timestamp":1722942619000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10456-024-09925-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,21]]},"references-count":79,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["9925"],"URL":"https:\/\/doi.org\/10.1007\/s10456-024-09925-9","relation":{},"ISSN":["0969-6970","1573-7209"],"issn-type":[{"value":"0969-6970","type":"print"},{"value":"1573-7209","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,21]]},"assertion":[{"value":"1 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 April 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 May 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 June 2024","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1007\/s10456-024-09932-w","URL":"https:\/\/doi.org\/10.1007\/s10456-024-09932-w","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Bojana Lazovic, Leif Wigge, Miguel Carracedo Ortiz, Franziska Kohl, Ramy Elgendy, Pratik Saxena, Xuechong Hong and Ryan Hicks are all AstraZeneca employees. Ryan Hicks is an AstraZeneca shareholder. Hoang-Tuan Nguyen, Jere Kettunen and Prateek Singh are all Finnadvance employees.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}