{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:52:40Z","timestamp":1791424360225,"version":"4.3.3"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T00:00:00Z","timestamp":1604188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Lymphangioleiomyomatosis (LAM) is a metastatic neoplasm of reproductive-age women associated with mutations in tuberous sclerosis complex genes. LAM causes cystic remodeling of the lung and progressive respiratory failure. The sources and cellular characteristics of LAM cells underlying disease pathogenesis remain elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Identification and characterization of LAM cells in human lung and uterus using a single-cell approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Single-cell and single-nuclei RNA sequencing on LAM (n\u2009=\u20094) and control (n\u2009=\u20097) lungs, immunofluorescence confocal microscopy, ELISA, and aptamer proteomics were used to identify and validate LAMCORE cells and secreted biomarkers, predict cellular origins, and define molecular and cellular networks in LAM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>A unique cell type termed LAMCORE was identified, which was distinct from, but closely related to, lung mesenchymal cells. LAMCORE cells expressing signature genes included known LAM markers such as PMEL, FIGF, CTSK, and MLANA and novel biomarkers validated by aptamer screening, ELISA, and immunofluorescence microscopy. LAM cells in lung and uterus are morphologically indistinguishable and share similar gene expression profiles and biallelic TSC2 mutations, supporting a potential uterine origin for the LAMCORE cell. Effects of LAM on resident pulmonary cell types indicated recruitment and activation of lymphatic endothelial cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A unique population of LAMCORE cells was identified in lung and uterus of patients with LAM, sharing close transcriptomic identity. LAM cell selective markers, secreted biomarkers, and the predicted cellular molecular features provide new insights into the signaling and transcriptional programs that may serve as diagnostic markers and therapeutic targets to influence the pathogenesis of LAM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201912-2445oc","type":"journal-article","created":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T17:47:33Z","timestamp":1593539253000},"page":"1373-1387","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":112,"title":["Single-Cell Transcriptomic Analysis Identifies a Unique Pulmonary Lymphangioleiomyomatosis Cell"],"prefix":"10.1093","volume":"202","author":[{"given":"Minzhe","family":"Guo","sequence":"first","affiliation":[{"name":"The Perinatal Institute and Section of Neonatology, Perinatal and Pulmonary Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane J.","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Karina","family":"Perl","sequence":"additional","affiliation":[{"name":"The Perinatal Institute and Section of Neonatology, Perinatal and Pulmonary Biology"},{"name":"Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn A.","family":"Wikenheiser-Brokamp","sequence":"additional","affiliation":[{"name":"The Perinatal Institute and Section of Neonatology, Perinatal and Pulmonary Biology"},{"name":"Division of Pathology and Laboratory Medicine, and"},{"name":"Department of Pathology and Laboratory Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Riccetti","sequence":"additional","affiliation":[{"name":"The Perinatal Institute and Section of Neonatology, Perinatal and Pulmonary Biology"},{"name":"Division of Developmental Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik Y.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parvathi","family":"Sudha","sequence":"additional","affiliation":[{"name":"The Perinatal Institute and Section of Neonatology, Perinatal and Pulmonary Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Adam","sequence":"additional","affiliation":[{"name":"Division of Developmental Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Potter","sequence":"additional","affiliation":[{"name":"Division of Developmental Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J.","family":"Kopras","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krinio","family":"Giannikou","sequence":"additional","affiliation":[{"name":"Cancer Genetics Laboratory, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Steven","family":"Potter","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"},{"name":"Division of Developmental Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue","family":"Sherman","sequence":"additional","affiliation":[{"name":"The LAM Foundation, Cincinnati, Ohio; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen R.","family":"Hammes","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, University of Rochester, Rochester, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Kwiatkowski","sequence":"additional","affiliation":[{"name":"Cancer Genetics Laboratory, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, 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