ArticleNature communications2020
mTORC1 activation in lung mesenchyme drives sex- and age-dependent pulmonary structure and function decline.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 57 citations in OpenAlex.
- Exploring glucocorticoid receptor signalling in lymphangioleiomyomatosis.ERJ open research · 2026Article
- BRD4 promotes endodermal cell fate during mammalian lung development.JCI insight · 2026Article
- Diagnostic Value of Serum VEGF-D in Lymphangioleiomyomatosis: Results of the First Prospective Study in the Russian Federation.Diagnostics (Basel, Switzerland) · 2026Article
- mTOR dysregulation induces IL-6 and paracrine AT2 cell senescence impeding lung repair in lymphangioleiomyomatosis.Nature communications · 2025Article
- LAM-CAM:American journal of respiratory cell and molecular biology · 2025Article
- Addressing Sex as a Biological Variable in Preclinical Models of Lung Disease: An Official American Thoracic Society Research Statement.American journal of respiratory and critical care medicine · 2025Article
- The Bi-steric Inhibitor RMC-5552 Reduces mTORC1 Signaling and Growth in Lymphangioleiomyomatosis.American journal of respiratory cell and molecular biology · 2025Article
- Lymphangioleiomyomatosis and Pregnancy-Do We Have All the Answers for a Woman Who Desires to Conceive?-Literature Review.Cancers · 2025Review
- The development for emerging biomarkers of lymphangioleiomyomatosis.Orphanet journal of rare diseases · 2024Review
- Triiodothyronine acts on DAO to regulate pulmonary fibrosis progression by facilitating cell senescence through the p53/p21 signaling pathway.Frontiers in pharmacology · 2024Article
- Hyperactive mTORC1 in lung mesenchyme induces endothelial cell dysfunction and pulmonary vascular remodeling.The Journal of clinical investigation · 2023Article
- Activation of mTOR signaling in adult lung microvascular progenitor cells accelerates lung aging.The Journal of clinical investigation · 2023Article
- Lost in translation: a neglected mTOR target for lymphangioleiomyomatosis.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Lymphangioleiomyomatosis: where endocrinology, immunology and tumor biology meet.Endocrine-related cancer · 2023Review
- Atf3 defines a population of pulmonary endothelial cells essential for lung regeneration.eLife · 2023Article
- Cell survival pathways targeted in rare lung disease affecting women.Science advances · 2023Review
- Estradiol Augments Tumor-Induced Neutrophil Production to Promote Tumor Cell Actions in Lymphangioleiomyomatosis Models.Endocrinology · 2023Article
- Lymphangioleiomyomatosis: a metastatic lung disease.American journal of physiology. Cell physiology · 2023Review
- Lymphangioleiomyomatosis (LAM) Cell Atlas.Thorax · 2023Article
- Midkine expression by stem-like tumor cells drives persistence to mTOR inhibition and an immune-suppressive microenvironment.Nature communications · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 4 institutions in 1 country.
Funding
Abstract
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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.