{"corpus_id":207914132,"paper_sha":"8f877e5c1444a90fa887a14bbd528230cf4b08a7","doi":"10.1007/s00401-019-02091-z","arxiv_id":null,"pmid":31696318,"pmcid":"6989586","mag_id":2983079328,"dblp_id":null,"acl_id":null,"title":"Structural and functional conservation of non-lumenized lymphatic endothelial cells in the mammalian leptomeninges","year":2019,"publication_date":"2019-11-06","venue":"Acta Neuropathologica","journal":{"name":"Acta Neuropathologica","pages":"383 - 401","volume":"139"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, N.I.H., Extramural","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":75,"citation_count":41,"influential_citation_count":6,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Adult","mj":false,"ui":"D000328"},{"d":"Aged","mj":false,"ui":"D000368"},{"d":"Aged, 80 and over","mj":false,"ui":"D000369"},{"d":"Amyloid beta-Peptides","mj":false,"ui":"D016229"},{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Brain","mj":false,"qs":[{"q":"pathology","mj":true,"ui":"Q000473"}],"ui":"D001921"},{"d":"Endothelial Cells","mj":false,"qs":[{"q":"pathology","mj":true,"ui":"Q000473"},{"q":"physiology","mj":true,"ui":"Q000502"}],"ui":"D042783"},{"d":"Female","mj":false,"ui":"D005260"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Lymphatic System","mj":false,"qs":[{"q":"pathology","mj":true,"ui":"Q000473"}],"ui":"D008208"},{"d":"Male","mj":false,"ui":"D008297"},{"d":"Meninges","mj":false,"qs":[{"q":"pathology","mj":true,"ui":"Q000473"}],"ui":"D008578"},{"d":"Mice","mj":false,"ui":"D051379"},{"d":"Zebrafish","mj":false,"ui":"D015027"}],"chemicals":[{"n":"Amyloid beta-Peptides","ui":"D016229","reg":"0"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://link.springer.com/content/pdf/10.1007/s00401-019-02091-z.pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/8f877e5c1444a90fa887a14bbd528230cf4b08a7","s2_open_access_license":"CCBY","s2_open_access_status":"HYBRID","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"The vertebrate CNS is surrounded by the meninges, a protective barrier comprised of the outer dura mater and the inner leptomeninges, which includes the arachnoid and pial layers. While the dura mater contains lymphatic vessels, no conventional lymphatics have been found within the brain or leptomeninges. However, non-lumenized cells called Brain/Mural Lymphatic Endothelial Cells or Fluorescent Granule Perithelial cells (muLECs/BLECs/FGPs) that share a developmental program and gene expression with peripheral lymphatic vessels have been described in the meninges of zebrafish. Here we identify a structurally and functionally similar cell type in the mammalian leptomeninges that we name Leptomeningeal Lymphatic Endothelial Cells (LLEC). As in zebrafish, LLECs express multiple lymphatic markers, containing very large, spherical inclusions, and develop independently from the meningeal macrophage lineage. Mouse LLECs also internalize macromolecules from the cerebrospinal fluid, including Amyloid-β, the toxic driver of Alzheimer’s disease progression. Finally, we identify morphologically similar cells co-expressing LLEC markers in human post-mortem leptomeninges. Given that LLECs share molecular, morphological, and functional characteristics with both lymphatics and macrophages, we propose they represent a novel, evolutionary conserved cell type with potential roles in homeostasis and immune organization of the meninges.","claims":[{"public_id":"cl_4cf3929a0253817f157d93bed437592b","status":"active","text":"A structurally and functionally similar non-lumenized lymphatic endothelial cell population exists in the mammalian leptomeninges and is named Leptomeningeal Lymphatic Endothelial Cells (LLEC).","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_4cf3929a0253817f157d93bed437592b"},{"public_id":"cl_8a9fc12d13ede4d5f65275139d1030e2","status":"active","text":"Leptomeningeal Lymphatic Endothelial Cells express multiple lymphatic markers, contain very large spherical inclusions, and develop independently from the meningeal macrophage lineage.","confidence":0.96,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_8a9fc12d13ede4d5f65275139d1030e2"},{"public_id":"cl_29331c767483bcc80d20219ddbbea728","status":"active","text":"Leptomeningeal Lymphatic Endothelial Cells represent a novel, evolutionarily conserved cell type with potential roles in meningeal homeostasis and immune organization.","confidence":0.92,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_29331c767483bcc80d20219ddbbea728"},{"public_id":"cl_7c5dce4edb5de666678b5b742e0e0744","status":"active","text":"Morphologically similar cells co-expressing Leptomeningeal Lymphatic Endothelial Cell markers are present in human post-mortem leptomeninges.","confidence":0.9,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_7c5dce4edb5de666678b5b742e0e0744"},{"public_id":"cl_bf1a9a3b1e3bf31e0754280dd52bb7fd","status":"active","text":"Mouse Leptomeningeal Lymphatic Endothelial Cells internalize macromolecules from cerebrospinal fluid, including Amyloid-β.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_bf1a9a3b1e3bf31e0754280dd52bb7fd"}],"concepts":[{"public_id":"co_13f9cd0bedfe6eb54fd15b069236dc3c","status":"active","name":"homeostasis and immune organization","description":"Physiological maintenance and immune structuring functions proposed for the leptomeninges.","types":["biological 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(12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_5581b5d44757017fb4cd4ac4603c2526"},{"public_id":"co_56bc881229193bdb9a8cd96462718ad3","status":"active","name":"Leptomeningeal Lymphatic Endothelial Cells","description":"A non-lumenized cell population identified in the mammalian leptomeninges that expresses lymphatic-associated markers and shares features with lymphatic and macrophage-like cells.","types":["cell type"],"aliases":["LLEC"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_56bc881229193bdb9a8cd96462718ad3"},{"public_id":"co_72d056dcb0b08a94786882084216331b","status":"active","name":"cerebrospinal fluid","description":"The fluid surrounding the brain and spinal cord from which LLECs can internalize macromolecules.","types":["body 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