Identification of the lymphangioleiomyomatosis cell and its uterine origin
Identification of the lymphangioleiomyomatosis cell and its uterine origin
SUMMARY Lymphangioleiomyomatosis (LAM) is a metastasizing neoplasm of reproductive age women that causes cystic lung remodeling and progressive respiratory failure. The source of LAM cells that invade the lung and the reasons that LAM targets women have remained elusive. We employed single cell and single nuclei RNA sequencing on LAM lesions within explanted LAM lungs, known to contain smooth muscle like cells bearing mTOR activating mutations in TSC1 or TSC2, and identified a unique population of cells that were readily distinguished from those of endogenous lung cells. LAMCORE cells shared closest transcriptomic similarity to normal uterus and neural crest. Immunofluorescence microscopy demonstrated the expression of LAMCORE cell signature genes within LAM lesions in both lung and uterus. Serum aptamer proteomics and ELISA identified biomarkers predicted to be secreted by LAMCORE cells. Single cell transcriptomics strongly supports a uterine neural crest origin of LAMCORE cells; providing insights into disease pathogenesis and informing future treatment strategies for LAM. SIGNIFICANCEPresent study identified a novel population of LAMCORE cells, which is likely originated from uterine neural crest; identified novel LAM cell-specific secretome proteins that hold promise as potential biomarkers and therapeutic targets. Advancing the understanding of LAM pathogenesis and metastasis model may yield broader insights into the biology of cancer.
Kwiatkowski David J.、Yu Jane J.、Zhang Erik Y.、Sudha Parvathi、Adam Mike、Potter S Steven、Sherman Sue、Potter Andrew、Wikenheiser-Brokamp Kathryn A.、Kopras Elizabeth J.、Perl Anne Karina、Hammes Stephen R.、Giannikou Krinio、Whitsett Jeffrey A.、Xu Yan、Guo Minzhe、McCormack Francis X.、Riccetti Matt
Department of Medicine, Brigham and Women?ˉs Hospital and Harvard Medical SchoolDivision of Pulmonary, Critical Care and Sleep Medicine, University of Cincinnati School of MedicineDivision of Pulmonary, Critical Care and Sleep Medicine, University of Cincinnati School of MedicineThe Perinatal Institute and Section of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children?ˉs Hospital Medical CenterDivision of Developmental Biology, Cincinnati Children?ˉs Hospital Medical CenterDivision of Developmental Biology, Cincinnati Children?ˉs Hospital Medical Center||Department of Pediatrics, University of Cincinnati School of MedicineThe LAM Foundation, CincinnatiDivision of Developmental Biology, Cincinnati Children?ˉs Hospital Medical CenterThe Perinatal Institute and Section of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children?ˉs Hospital Medical Center||Division of Pathology & Laboratory Medicine, Cincinnati Children?ˉs Hospital Medical Center||Department of Pathology & Laboratory Medicine, University of Cincinnati School of MedicineDivision of Pulmonary, Critical Care and Sleep Medicine, University of Cincinnati School of MedicineThe Perinatal Institute and Section of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children?ˉs Hospital Medical Center||Department of Pediatrics, University of Cincinnati School of MedicineDivision of Endocrinology and Metabolism, University of RochesterDepartment of Medicine, Brigham and Women?ˉs Hospital and Harvard Medical SchoolThe Perinatal Institute and Section of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children?ˉs Hospital Medical Center||Department of Pediatrics, University of Cincinnati School of MedicineThe Perinatal Institute and Section of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children?ˉs Hospital Medical Center||Department of Biomedical Informatics, University of Cincinnati School of Medicine||Department of Pediatrics, University of Cincinnati School of MedicineThe Perinatal Institute and Section of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children?ˉs Hospital Medical CenterDivision of Pulmonary, Critical Care and Sleep Medicine, University of Cincinnati School of MedicineThe Perinatal Institute and Section of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children?ˉs Hospital Medical Center||Division of Developmental Biology, Cincinnati Children?ˉs Hospital Medical Center
基础医学肿瘤学细胞生物学
lymphangioleiomyomatosislungsingle cell analysisoriginuterus
Kwiatkowski David J.,Yu Jane J.,Zhang Erik Y.,Sudha Parvathi,Adam Mike,Potter S Steven,Sherman Sue,Potter Andrew,Wikenheiser-Brokamp Kathryn A.,Kopras Elizabeth J.,Perl Anne Karina,Hammes Stephen R.,Giannikou Krinio,Whitsett Jeffrey A.,Xu Yan,Guo Minzhe,McCormack Francis X.,Riccetti Matt.Identification of the lymphangioleiomyomatosis cell and its uterine origin[EB/OL].(2025-03-28)[2025-05-23].https://www.biorxiv.org/content/10.1101/784199.点此复制
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