lung   284

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JCI - Modeling metastasis biology and therapy in real time in the mouse lung
Lung slice culture - use agar insufflation

Pulmonary metastasis remains the leading ca use of death for cancer patients. Opportunities to improve treatment outcomes for patients require new methods to study and view the biology of metastatic progression. Here, we describe an ex vivo pulmonary metastasis assay (PuMA) in which the metastatic progression of GFP-expressing cancer cells, from a single cell to the formation of multicellular colonies, in the mouse lung microenvironment was assessed in real time for up to 21 days. The biological validity of this assay was confirmed by its prediction of the in vivo behavior of a variety of high- and low-metastatic human and mouse cancer cell lines and the discrimination of tumor microenvironments in the lung that were most permissive to metastasis. Using this approach, we provide what we believe to be new insights into the importance of tumor cell interactions with the stromal components of the lung microenvironment. Finally, the translational utility of this assay was demonstrated through its use in the evaluation of therapeutics at discrete time points during metastatic progression. We believe that this assay system is uniquely capable of advancing our understanding of both metastasis biology and therapeutic strategies.
lung  slices  in_vitro  Metastasis 
8 weeks ago by Segalllab
Lung Single-Cell Signaling Interaction Map Reveals Basophil Role in Macrophage Imprinting - ScienceDirect
lung basophils can polarize macrophages to M2

Lung development and function arises from the interactions between diverse cell types and lineages. Using single-cell RNA sequencing (RNA-seq), we characterize the cellular composition of the lung during development and identify vast dynamics in cell composition and their molecular characteristics. Analyzing 818 ligand-receptor interaction pairs within and between cell lineages, we identify broadly interacting cells, including AT2, innate lymphocytes (ILCs), and basophils. Using interleukin (IL)-33 receptor knockout mice and in vitro experiments, we show that basophils establish a lung-specific function imprinted by IL-33 and granulocyte-macrophage colony-stimulating factor (GM-CSF), characterized by unique signaling of cytokines and growth factors important for stromal, epithelial, and myeloid cell fates. Antibody-depletion strategies, diphtheria toxin-mediated selective depletion of basophils, and co-culture studies show that lung resident basophils are important regulators of alveolar macrophage development and function. Together, our study demonstrates how whole-tissue signaling interaction map on the single-cell level can broaden our understanding of cellular networks in health and disease.
macrophage_polarization  M2_macrophages  lung  basophils 
10 weeks ago by Segalllab
Interstitial Lung Abnormality
An ILA refers to a subtle or mild parenchymal abnormality identified in more than 5% of lungs on CT scans in patients in whom interstitial lung disease was not previously clinically suspected
lung  chest  ct 
january 2019 by observer1959
Vav3-induced cytoskeletal dynamics contribute to heterotypic properties of endothelial barriers | JCB
Partial characterizaiton of multiple types of endothelium that was purchased using nanostring for 283 genes. Also single cell RNAseq for lung so lung endothelium at greater depth

Through multiple cell–cell and cell–matrix interactions, epithelial and endothelial sheets form tight barriers. Modulators of the cytoskeleton contribute to barrier stability and act as rheostats of vascular permeability. In this study, we sought to identify cytoskeletal regulators that underlie barrier diversity across vessels. To achieve this, we correlated functional and structural barrier features to gene expression of endothelial cells (ECs) derived from different vascular beds. Within a subset of identified candidates, we found that the guanosine nucleotide exchange factor Vav3 was exclusively expressed by microvascular ECs and was closely associated with a high-resistance barrier phenotype. Ectopic expression of Vav3 in large artery and brain ECs significantly enhanced barrier resistance and cortical rearrangement of the actin cytoskeleton. Mechanistically, we found that the barrier effect of Vav3 is dependent on its Dbl homology domain and downstream activation of Rap1. Importantly, inactivation of Vav3 in vivo resulted in increased vascular leakage, highlighting its function as a key regulator of barrier stability.
endothelium  gene_expression  single_cell_rnaseq  lung 
january 2019 by Segalllab
Amphiregulin-Producing Pathogenic Memory T Helper 2 Cells Instruct Eosinophils to Secrete Osteopontin and Facilitate Airway Fibrosis: Immunity
Osteopontin production is also correlated with worse outcome in breast cancer - possible mechanism for areg to increase metastasis through fibrosis driven by areg stimulation of eosinophils?

We found that interleukin-33 (IL-33) enhanced amphiregulin production by the IL-33 receptor, ST2hi memory T helper 2 (Th2) cells. Amphiregulin-epidermal growth factor receptor (EGFR)-mediated signaling directly reprogramed eosinophils to an inflammatory state with enhanced production of osteopontin, a key profibrotic immunomodulatory protein. IL-5-producing memory Th2 cells and amphiregulin-producing memory Th2 cells appeared to cooperate to establish lung fibrosis. The analysis of polyps from patients with eosinophilic chronic rhinosinusitis revealed fibrosis with accumulation of amphiregulin-producing CRTH2hiCD161hiCD45RO+CD4+ Th2 cells and osteopontin-producing eosinophils. Thus, the IL-33-amphiregulin-osteopontin axis directs fibrotic responses in eosinophilic airway inflammation and is a potential target for the treatment of fibrosis induced by chronic allergic disorders.
AREG  fibrosis  lung  eosinophil  osteopontin 
december 2018 by Segalllab
How to Increase Lung Capacity: Breathing Exercises
COPD can significantly reduce lung function. Learn how to increase lung capacity with these easy breathing exercises.
breathing  techniques  lung  exercises 
october 2018 by thejaymo
A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte | Nature
have rnaseq for different categories - kif9 up in ciliated and one or two others

here we perform single-cell profiling of human bronchial epithelial cells and mouse tracheal epithelial cells to obtain a comprehensive census of cell types in the conducting airway and their behaviour in homeostasis and regeneration. Our analysis reveals cell states that represent known and novel cell populations, delineates their heterogeneity and identifies distinct differentiation trajectories during homeostasis and tissue repair. Finally, we identified a novel, rare cell type that we call the ‘pulmonary ionocyte’, which co-expresses FOXI1, multiple subunits of the vacuolar-type H+-ATPase (V-ATPase) and CFTR, the gene that is mutated in cystic fibrosis. Using immunofluorescence, modulation of signalling pathways and electrophysiology, we show that Notch signalling is necessary and FOXI1 expression is sufficient to drive the production of the pulmonary ionocyte, and that the pulmonary ionocyte is a major source of CFTR activity in the conducting airway epithelium.
lung  multciliated_cells  kif9 
august 2018 by Segalllab
Pazienti con la mutazione Ros-1, supereroi in cerca di una cura -
Da un gruppo di pazienti con la mutazione Ros-1 è nato negli Stati Uniti e – grazie ai social network – si sta diffondendo in tutto il mondo, Italia incluso, un network di pazienti disposti a fornire campioni del loro tessuto per una sperimentazione clinica. E’ il primo caso di ricerca che nasce direttamente dai pazienti
healthcare  cancer  lung  ROS-1  patient  counterpoint  social-net 
june 2018 by PieroRivizzigno

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