Project description:In dogs, a species for which markers of cell populations are often limiting, we sought to evaluate in an unbiased way the heterogeneity of cell subpopulations in the bronchoalveolar lavage fluid of healthy dogs, by single-cell RNA-sequencing.
Project description:Many lung diseases remain understudied due to a lack of experimental models. Lung organoids, which consist of self-organizing epithelial cells, provide versatile in vitro models for normal and abnormal biology, drug screening, gene editing, and personalized therapeutics. However, human organoids are generally derived from lung tissue, which is not commonly obtained and represents only a small fraction of lung pathologies. Induced pluripotent stem cells have provided an important alternative but require complex manipulation. Recently, one study reported airway organoids from bronchoalveolar lavage (BAL) fluid, though sample sizes and characterization were limited. Here, we demonstrate robust establishment of airway organoids from a variety of human BAL samples and show that these organoids consist predominantly of basal cells plus differentiated airway cell types including secretory, ciliated, KRT13+ “hillock,” and ionocyte cells. Furthermore, we report the development of BAL-derived alveolar organoids comprised of alveolar type 2 (AT2) cells. These techniques significantly expand the scope of lung diseases that can be studied using safely accessible primary human cells.
Project description:Bronchoalveolar Lavage cells include resident and infiltrating immune cells in repsone to infections. We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of BALF cells.
Project description:CX3CR1pos monocytes are mobilized upon infection and undergo monocyte-to-macrophage transition in inflamed tissues. Using scRNA-seq of CD11c+ cells from bronchoalveolar lavage fluid (BALF) infected with IAV (PR/8, H1N1 ,we demonstrate that, during severe viral pneumonia, bone marrow-derived macrophages (BMDM) pass co-ordinated trajectories of pro-inflammatory-to-tissue-healing phenotypes, before differentiating into tissue-resident alveolar macrophages, that retain a long-term tissue-protective phenotype.