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While\n                      <jats:italic>FZD4<\/jats:italic>\n                      mutations are established genetic causes of FEVR, the molecular mechanisms underlying pathological neovascularisation remain poorly understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      CRISPR\/Cas9 was used to generate the\n                      <jats:italic>Fzd4<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>M105V<\/jats:italic>\n                      <\/jats:sup>\n                      mouse model. Comprehensive vascular phenotyping entailed retinal wholemount imaging, analysis of hyaloid vessel regression and immunohistochemical evaluation of the deep retinal vasculature. Flow cytometry sorting and single\u2010cell RNA sequencing (scRNA\u2010seq) were used to characterise the expression profiles of retinal endothelial cells (ECs) in mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>FZD4<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>M105V<\/jats:italic>\n                      <\/jats:sup>\n                      model recapitulated key FEVR features including retinal aneurysmal vessels in adult mice, developmental abnormalities in juveniles, impaired deep vascular formation, delayed hyaloid regression, vascular leakage and reduced endothelial proliferation. ScRNA\u2010seq revealed distinct transcriptional profiles in pathological EC clusters and tip cells. KEGG analysis revealed that the EC clusters were enriched in focal adhesion, Rap1, PI3K\u2010Akt and apelin signalling pathways, whereas tip cells were enriched in the VEGF, chemokine, NF\u2010\u03baB and TNF signalling pathways. We further identified four novel candidate markers of pathological neovascularisation:\n                      <jats:italic>Ctss<\/jats:italic>\n                      ,\n                      <jats:italic>Ccl4<\/jats:italic>\n                      ,\n                      <jats:italic>Ccl3<\/jats:italic>\n                      and\n                      <jats:italic>Apoe.<\/jats:italic>\n                      Subsequent validation confirmed the upregulation of CTSS and CCL4 within neovascular lesions, supporting their functional role in pathological angiogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We established a novel mouse model of pathological neovascularisation with a missense mutation and elucidated the expression profiles of retinal ECs. The identified pathways and novel biomarkers\u2010particularly CTSS and CCL4\u2010provide new insights for further pathogenesis investigation of FEVR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ceo.70011","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T23:49:51Z","timestamp":1760658591000},"page":"113-126","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unveiling Endothelial Cell Expression Profiles in\n                    <scp>FEVR<\/scp>\n                    : Identification of Key Genes Associated With Pathological Neovascularisation in a\n                    <scp>\n                      <i>FZD4<\/i>\n                      <sup>\n                        <i>M105V<\/i>\n                      <\/sup>\n                    <\/scp>\n                    Mouse Model"],"prefix":"10.1111","volume":"54","author":[{"given":"Huijuan","family":"Xu","sequence":"first","affiliation":[{"name":"The Genetic Diseases Key Laboratory of Sichuan Province, The Department of Medical Genetics, The Department of Laboratory Medicine, Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital, School of Medicine University of Electronic Science and Technology of China  Chengdu China"},{"name":"Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026) Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunqi","family":"He","sequence":"additional","affiliation":[{"name":"The Genetic Diseases Key Laboratory of Sichuan Province, The Department of Medical Genetics, The Department of Laboratory Medicine, Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital, School of Medicine University of Electronic Science and Technology of China  Chengdu China"},{"name":"Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026) Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianjun","family":"Zhu","sequence":"additional","affiliation":[{"name":"The Genetic Diseases Key Laboratory of Sichuan Province, The Department of Medical Genetics, The Department of Laboratory Medicine, Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital, School of Medicine University of Electronic Science and Technology of China  Chengdu China"},{"name":"Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026) Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital  Chengdu Sichuan 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