Integrated Single-Cell Atlas of Endothelial Cells of the Human Lung.

Autor:	Schupp JC; Pulmonary, Critical Care and Sleep Medicine (J.C.S., T.S.A., C.C., N.O., M.C., K.-A.R., E.P.M., M.S., G.D., F.A., N.N., X.Y., N.K.), Yale University School of Medicine, New Haven, CT., Adams TS; Pulmonary, Critical Care and Sleep Medicine (J.C.S., T.S.A., C.C., N.O., M.C., K.-A.R., E.P.M., M.S., G.D., F.A., N.N., X.Y., N.K.), Yale University School of Medicine, New Haven, CT., Cosme C Jr; Pulmonary, Critical Care and Sleep Medicine (J.C.S., T.S.A., C.C., N.O., M.C., K.-A.R., E.P.M., M.S., G.D., F.A., N.N., X.Y., N.K.), Yale University School of Medicine, New Haven, CT., Raredon MSB; Department of Biomedical Engineering (M.S.B.R., L.E.N.), Yale University, New Haven, CT.; Vascular Biology and Therapeutics (M.S.B.R., Y.Y., L.E.N.), Yale University, New Haven, CT., Yuan Y; Vascular Biology and Therapeutics (M.S.B.R., Y.Y., L.E.N.), Yale University, New Haven, CT.; Department of Anesthesiology (Y.Y., L.E.N.), Yale University, New Haven, CT., Omote N; Pulmonary, Critical Care and Sleep Medicine (J.C.S., T.S.A., C.C., N.O., M.C., K.-A.R., E.P.M., M.S., G.D., F.A., N.N., X.Y., N.K.), Yale University School of Medicine, New Haven, CT., Poli S; Department of Medicine, Baylor College of Medicine, Houston, TX (S.P., I.O.R.).; Division of Internal Medicine, Mount Sinai Medical Center, Miami Beach, FL (S.P.)., Chioccioli M; Pulmonary, Critical Care and Sleep Medicine (J.C.S., T.S.A., C.C., N.O., M.C., K.-A.R., E.P.M., M.S., G.D., F.A., N.N., X.Y., N.K.), Yale University School of Medicine, New Haven, CT., Rose KA; Pulmonary, Critical Care and Sleep Medicine (J.C.S., T.S.A., C.C., N.O., M.C., K.-A.R., E.P.M., M.S., G.D., F.A., N.N., X.Y., N.K.), Yale University School of Medicine, New Haven, CT., Manning EP; Pulmonary, Critical Care and Sleep Medicine (J.C.S., T.S.A., C.C., N.O., M.C., K.-A.R., E.P.M., M.S., G.D., F.A., N.N., X.Y., N.K.), Yale University School of Medicine, New Haven, CT.; VA Connecticut Healthcare System (E.P.M.), West Haven., Sauler M; Pulmonary, Critical Care and Sleep Medicine (J.C.S., T.S.A., C.C., N.O., M.C., K.-A.R., E.P.M., M.S., G.D., F.A., N.N., X.Y., N.K.), Yale University School of Medicine, New Haven, CT., DeIuliis G; Pulmonary, Critical Care and Sleep Medicine (J.C.S., T.S.A., C.C., N.O., M.C., K.-A.R., E.P.M., M.S., G.D., F.A., N.N., X.Y., N.K.), Yale University School of Medicine, New Haven, CT., Ahangari F; Pulmonary, Critical Care and Sleep Medicine (J.C.S., T.S.A., C.C., N.O., M.C., K.-A.R., E.P.M., M.S., G.D., F.A., N.N., X.Y., N.K.), Yale University School of Medicine, New Haven, CT., Neumark N; Pulmonary, Critical Care and Sleep Medicine (J.C.S., T.S.A., C.C., N.O., M.C., K.-A.R., E.P.M., M.S., G.D., F.A., N.N., X.Y., N.K.), Yale University School of Medicine, New Haven, CT., Habermann AC; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (A.C.H., J.A.K.)., Gutierrez AJ; Translational Genomics Research Institute, Phoenix, AZ (A.J.G., L.T.B., N.E.B.)., Bui LT; Translational Genomics Research Institute, Phoenix, AZ (A.J.G., L.T.B., N.E.B.)., Lafyatis R; Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, PA (R.L.)., Pierce RW; Department of Pediatrics (R.W.P.), Yale University School of Medicine, New Haven, CT., Meyer KB; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK (K.B.M., S.A.T.)., Nawijn MC; Department of Pathology and Medical Biology (M.C.N.), University Medical Center Groningen, University of Groningen, The Netherlands.; Groningen Research Institute for Asthma and COPD (M.C.N.), University Medical Center Groningen, University of Groningen, The Netherlands., Teichmann SA; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK (K.B.M., S.A.T.).; Theory of Condensed Matter Group, Cavendish Laboratory/Department of Physics, University of Cambridge, UK (S.A.T.)., Banovich NE; Translational Genomics Research Institute, Phoenix, AZ (A.J.G., L.T.B., N.E.B.)., Kropski JA; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (A.C.H., J.A.K.).; Department of Veterans Affairs Medical Center, Nashville, TN (J.A.K.).; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN (J.A.K.)., Niklason LE; Department of Biomedical Engineering (M.S.B.R., L.E.N.), Yale University, New Haven, CT.; Vascular Biology and Therapeutics (M.S.B.R., Y.Y., L.E.N.), Yale University, New Haven, CT.; Department of Anesthesiology (Y.Y., L.E.N.), Yale University, New Haven, CT., Pe'er D; Program for Computational and Systems Biology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (D.P.)., Yan X; Pulmonary, Critical Care and Sleep Medicine (J.C.S., T.S.A., C.C., N.O., M.C., K.-A.R., E.P.M., M.S., G.D., F.A., N.N., X.Y., N.K.), Yale University School of Medicine, New Haven, CT., Homer RJ; Department of Pathology (R.J.H.), Yale University School of Medicine, New Haven, CT.; Pathology and Laboratory Medicine Service (R.J.H.), West Haven., Rosas IO; Department of Medicine, Baylor College of Medicine, Houston, TX (S.P., I.O.R.)., Kaminski N; Pulmonary, Critical Care and Sleep Medicine (J.C.S., T.S.A., C.C., N.O., M.C., K.-A.R., E.P.M., M.S., G.D., F.A., N.N., X.Y., N.K.), Yale University School of Medicine, New Haven, CT.
Jazyk:	angličtina
Zdroj:	Circulation [Circulation] 2021 Jul 27; Vol. 144 (4), pp. 286-302. Date of Electronic Publication: 2021 May 25.
DOI:	10.1161/CIRCULATIONAHA.120.052318
Abstrakt:	Background: Cellular diversity of the lung endothelium has not been systematically characterized in humans. We provide a reference atlas of human lung endothelial cells (ECs) to facilitate a better understanding of the phenotypic diversity and composition of cells comprising the lung endothelium. Methods: We reprocessed human control single-cell RNA sequencing (scRNAseq) data from 6 datasets. EC populations were characterized through iterative clustering with subsequent differential expression analysis. Marker genes were validated by fluorescent microscopy and in situ hybridization. scRNAseq of primary lung ECs cultured in vitro was performed. The signaling network between different lung cell types was studied. For cross-species analysis or disease relevance, we applied the same methods to scRNAseq data obtained from mouse lungs or from human lungs with pulmonary hypertension. Results: Six lung scRNAseq datasets were reanalyzed and annotated to identify >15 000 vascular EC cells from 73 individuals. Differential expression analysis of EC revealed signatures corresponding to endothelial lineage, including panendothelial, panvascular, and subpopulation-specific marker gene sets. Beyond the broad cellular categories of lymphatic, capillary, arterial, and venous ECs, we found previously indistinguishable subpopulations; among venous EC, we identified 2 previously indistinguishable populations: pulmonary-venous ECs (COL15A1 neg ) localized to the lung parenchyma and systemic-venous ECs (COL15A1 pos ) localized to the airways and the visceral pleura; among capillary ECs, we confirmed their subclassification into recently discovered aerocytes characterized by EDNRB , SOSTDC1 , and TBX2 and general capillary EC. We confirmed that all 6 endothelial cell types, including the systemic-venous ECs and aerocytes, are present in mice and identified endothelial marker genes conserved in humans and mice. Ligand-receptor connectome analysis revealed important homeostatic crosstalk of EC with other lung resident cell types. scRNAseq of commercially available primary lung ECs demonstrated a loss of their native lung phenotype in culture. scRNAseq revealed that endothelial diversity is maintained in pulmonary hypertension. Our article is accompanied by an online data mining tool (www.LungEndothelialCellAtlas.com). Conclusions: Our integrated analysis provides a comprehensive and well-crafted reference atlas of ECs in the normal lung and confirms and describes in detail previously unrecognized endothelial populations across a large number of humans and mice.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu