Project description:We performed global transcriptomic profiling of hALOs at early (P4), middle (P13) and late (P20) passages and found that the transcripts of the hALOs were similar to that of primary lung progenitor organoids.hALOs highly expressed genes associated with lung development/lung progenitor, AT2 specification and AT1 specification.We found that our hALOs were more similar to pseudoglandular-staged lung.The gene sets associated with alveolar maturation, such as surfactant homeostasis or response to oxygen levels, were upregulated in P20. Besides, genes involved in endoderm development or respiratory tube development were downregulated
Project description:Alveolar type 2 (AT2) cells function as stem cells in the adult lung and aid in injury-repair. The current study aimed to understand the signaling events that control differentiation of this therapeutically relevant cell type during human development through differentiation of lung progenitor organoids to AT2 cells and benchmarking against primary AT2 organoids.
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:We performed unbiased transcriptomic profiling on organoids cultures after SARS-CoV-2 infection to gain insights into AT2s response to SARS-CoV-2 infection.
Project description:We developed an in vitro model of pulmonary fibrosis using alveolar organoids, consisting of human induced pluripotent stem cell-derived alveolar epithelial cells and human lung fibroblasts. In this model, fibroblasts were activated by bleomysin (BLM) treatment in an epithelial cell-dependent manner simillar to the pathogenic mechanism of pulmonary fibrosis.
Project description:Human induced pluripotent stem cells (hiPSCs) were differentiated into alveolar epithelial cells in the fibroblast-dependent (FD) or fibroblast-free (FF) alveolar organoids (AO). Then the epithelial cells in FD-AOs or FF-AOs were subjected to scRNA-seq. Then, human iPSC-derived AT1 (iAT1) cells were demonstrated to be included in FD-AOs, not in FF-AOs. In addition, XAV-939 increased iAT1 cell population in FD-AOs.
Project description:We developed an in vitro model of pulmonary fibrosis using alveolar organoids, consisting of human induced pluripotent stem cell-derived alveolar epithelial cells and human lung fibroblasts. In this model, fibroblasts were activated by bleomysin (BLM) treatment in an epithelial cell-dependent manner simillar to the pathogenic mechanism observed in pulmonary fibrosis.