| http://purl.uniprot.org/citations/33159078 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33159078 | http://www.w3.org/2000/01/rdf-schema#comment | "Lymphangioleiomyomatosis (LAM) is a rare fatal cystic lung disease due to bi-allelic inactivating mutations in tuberous sclerosis complex (TSC1/TSC2) genes coding for suppressors of the mechanistic target of rapamycin complex 1 (mTORC1). The origin of LAM cells is still unknown. Here, we profile a LAM lung compared to an age- and sex-matched healthy control lung as a hypothesis-generating approach to identify cell subtypes that are specific to LAM. Our single-cell RNA sequencing (scRNA-seq) analysis reveals novel mesenchymal and transitional alveolar epithelial states unique to LAM lung. This analysis identifies a mesenchymal cell hub coordinating the LAM disease phenotype. Mesenchymal-restricted deletion of Tsc2 in the mouse lung produces a mTORC1-driven pulmonary phenotype, with a progressive disruption of alveolar structure, a decline in pulmonary function, increase of rapamycin-sensitive expression of WNT ligands, and profound female-specific changes in mesenchymal and epithelial lung cell gene expression. Genetic inactivation of WNT signaling reverses age-dependent changes of mTORC1-driven lung phenotype, but WNT activation alone in lung mesenchyme is not sufficient for the development of mouse LAM-like phenotype. The alterations in gene expression are driven by distinctive crosstalk between mesenchymal and epithelial subsets of cells observed in mesenchymal Tsc2-deficient lungs. This study identifies sex- and age-specific gene changes in the mTORC1-activated lung mesenchyme and establishes the importance of the WNT signaling pathway in the mTORC1-driven lung phenotype."xsd:string |
| http://purl.uniprot.org/citations/33159078 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41467-020-18979-4"xsd:string |
| http://purl.uniprot.org/citations/33159078 | http://purl.uniprot.org/core/author | "Li S."xsd:string |
| http://purl.uniprot.org/citations/33159078 | http://purl.uniprot.org/core/author | "Kopp M."xsd:string |
| http://purl.uniprot.org/citations/33159078 | http://purl.uniprot.org/core/author | "Beers M.F."xsd:string |
| http://purl.uniprot.org/citations/33159078 | http://purl.uniprot.org/core/author | "Lin S.M."xsd:string |
| http://purl.uniprot.org/citations/33159078 | http://purl.uniprot.org/core/author | "Morley M.P."xsd:string |
| http://purl.uniprot.org/citations/33159078 | http://purl.uniprot.org/core/author | "Evans J.F."xsd:string |
| http://purl.uniprot.org/citations/33159078 | http://purl.uniprot.org/core/author | "Atochina-Vasserman E.N."xsd:string |
| http://purl.uniprot.org/citations/33159078 | http://purl.uniprot.org/core/author | "Cantu E."xsd:string |
| http://purl.uniprot.org/citations/33159078 | http://purl.uniprot.org/core/author | "Morrisey E.E."xsd:string |
| http://purl.uniprot.org/citations/33159078 | http://purl.uniprot.org/core/author | "Babu A."xsd:string |
| http://purl.uniprot.org/citations/33159078 | http://purl.uniprot.org/core/author | "Frank D.B."xsd:string |
| http://purl.uniprot.org/citations/33159078 | http://purl.uniprot.org/core/author | "Sivakumar A."xsd:string |
| http://purl.uniprot.org/citations/33159078 | http://purl.uniprot.org/core/author | "Krymskaya V.P."xsd:string |
| http://purl.uniprot.org/citations/33159078 | http://purl.uniprot.org/core/author | "Robichaud A."xsd:string |
| http://purl.uniprot.org/citations/33159078 | http://purl.uniprot.org/core/author | "Carl J."xsd:string |
| http://purl.uniprot.org/citations/33159078 | http://purl.uniprot.org/core/author | "Rue R."xsd:string |
| http://purl.uniprot.org/citations/33159078 | http://purl.uniprot.org/core/author | "Obraztsova K."xsd:string |
| http://purl.uniprot.org/citations/33159078 | http://purl.uniprot.org/core/author | "Katzen J."xsd:string |
| http://purl.uniprot.org/citations/33159078 | http://purl.uniprot.org/core/author | "Mukhitov A.R."xsd:string |
| http://purl.uniprot.org/citations/33159078 | http://purl.uniprot.org/core/author | "Basil M.C."xsd:string |
| http://purl.uniprot.org/citations/33159078 | http://purl.uniprot.org/core/author | "Gritsiuta A.I."xsd:string |
| http://purl.uniprot.org/citations/33159078 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |