Alveolar organoid model
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA683600 | ENA |
REPOSITORIES: ENA
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Project description:Rationale: Alveolar epithelial type 2 (AT2) cells are stem/progenitor cells in the adult lung and their maintenance and regulation is achieved through their interaction with mesenchymal cells which constitute their niches. However, the precise identity of the niche cells is still elusive. Objectives: To characterize the niche cells capable of supporting the self-renewal of AT2 stem cells in the murine model. Methods: The alveolar organoid model was used to test the efficiency of different subpopulations of mesenchymal cells isolated by FACS from well-established (PdgfraGFP, Axin2LacZ, Fgf10LacZ) reporter mice to support the self-renewal of mature AT2 cells. The reporter-positive cells where pre-sorted based on Cd45neg Cd31neg Epcamneg Sca1pos. Additional selection was achieved using LipidTOX staining for cells containing high level of neutral lipids. Organoid size and colony formation efficiency after 2 weeks in culture were quantified. RNAscope combined with immunofluorescence on adult lungs. qPCR, gene array were used to characterize the niche cells. Measurements and main results: A subset of Sca1+; Fgf10-expressing cells positive for LipidTox staining in the distal mesenchyme is efficient in the self-renewal and differentiation of AT2 stem cells. Co-staining of adult lung by using ISH and IF staining for Fgf10 and Sftpc respectively, indicate that 28% of Fgf10+ cells are located to close to AT2 cells. These cells do not overlap with Fgf7-expressing cells. Gene array comparing MANC (Cd45Neg Cd31Neg EpcamNeg Sca1Pos Axin2LacZ/FDGPos) with Fgf10Pos Lipofibroblasts (Cd45Neg Cd31Neg EpcamNeg Sca1Pos Fgf10LacZ/FDGPos) support that these two cell subsets are different and express differential markers that can be further used for the respective characterization of these cells. Conclusions: We have demonstrated for the first time that Fgf10Pos LIF cells play important role to support AT2 stem cells in terms of self-renewal and differentiation toward the AT1 cell type. These cells appear different from the previously characterized MANC and display a similar activity in eliciting AT2 self-renewal.
2021-12-01 | GSE162859 | GEO
Project description:Chronic obstructive pulmonary disease (COPD) is characterized by inflammation and emphysema, leading to progressive alveolar destruction. Currently, no therapies effectively regenerate the alveolar epithelium. Here, we developed and characterized a feeder- and serum-free primary adult human organoid model to investigate how inflammatory conditions influence alveolar regeneration. Using Wnt activation and heregulin-β, we achieved long-term expansion of progenitor cells, while AT2 maturation protocols enhanced surfactant production, including the formation of tubular myelin. Introducing a LATS inhibitor to the expansion conditions induced an AT1 differentiation program without eliminating AT2 cells. Single-cell RNA-sequencing revealed multipotent progenitor-like populations, reflecting a state of heightened plasticity associated with regeneration. To model the effects of inflammation, we exposed these organoids to cytokines elevated in COPD. Notably, interferon-gamma (IFN-γ) exerted distinct effects on AT1 and AT2 cells: while it was cytotoxic to AT1 cells, it promoted growth in regenerating AT2 cells in a dose- and time-dependent manner. These findings underscore the nuanced influence of pro-inflammatory cytokines on alveolar regeneration. Our organoid model provides a reductionist platform for mechanistic studies in human cells, aiming to identify therapies that prevent alveolar destruction and improve alveolar regeneration in COPD
2026-03-09 | GSE287209 | GEO
Project description:The goal of this study was to investigate the transcriptional and epigenetic changes after the onset of KrasG12D and P53 Loss in Alveolar type 2 (AT2) cells using organoid model. Single cell Multi-omic sequencing were performed on 7 days tumor organoids which were derived from induced AT2 cells.
2025-08-31 | GSE227719 | GEO
Project description:A human organoid model of alveolar regeneration reveals distinct epithelial responses to interferon-gamma
| PRJNA1211630 | ENA
Project description:Nasal cell-derived alveolar organoid-macrophage co-culture
| PRJNA1405477 | ENA
Project description:Lower respiratory tract infection, such as pneumonia, is a significant threat to public health. We previously established human lung tissue-derived alveolar organoids (AlvO) as an in vitro model of alveolar epithelium for studying respiratory viruses. However, an advanced model is needed due to limited access to human lung tissues and the absence of immune cell components. Here, we developed novel protocols to generate physiological and functional alveolar organoids (nsoAlvO) from readily accessible and expandable nasal cell-derived organoids, and to generate alveolar macrophages (monoAM) from peripheral blood monocytes.
2026-08-19 | GSE316878 | GEO
Project description:Phosphoproteomic analysis of human alveolar organoids treated with TGF-β alone or in combination with monoclonal antibody/ASO
| PXD076548 |
Project description:Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and emphysema development, associated with enhanced tissue destruction and defective repair. Supporting cells in the alveolar niche play a crucial role in guiding the activation of alveolar epithelial progenitor cells during repair. Despite their close anatomical proximity, understanding of the supportive role of the pulmonary microvascular endothelium in adult alveolar epithelial repair remains limited. We hypothesized that angiocrine factors secreted by pulmonary endothelial cells support alveolar epithelial cell growth. Here, we report that human pulmonary microvasculature endothelial cells (HPMECs) support murine and human alveolar organoid formation through paracrine signaling via the secretion of extracellular vesicles and soluble factors. Transcriptomic and proteomic analysis pinpointed HPMEC-derived bone morphogenetic protein 6 (BMP6) as a critical factor for alveolar organoid formation. BMP6 deficiency was associated with reduced Wnt signaling and augmented oxidative stress signaling in murine lung tissue. Furthermore, BMP6 promoted alveolar epithelial cell growth, whereas function-blocking antibodies targeting BMP6 inhibited the beneficial effect of endothelial cells on murine alveolar organoid formation. Taken together, our findings highlight BMP6 as a key regulator of adult epithelial repair and suggest its potential as a therapeutic target for lung repair, particularly in individuals with COPD.
2026-07-02 | PXD053755 | Pride
Project description:Alveolar epithelial regeneration is critical for normal lung function and becomes dysregulated in disease. While alveolar type 2 (AT2) and club cells are known distal lung epithelial progenitors, determining if alveolar epithelial type 1 (AT1) cells also contribute to alveolar regeneration has been hampered by lack of highly specific mouse models labeling AT1 cells. To address this, the Gramd2CreERT2 transgenic strain was generated and crossed to ROSAmTmG mice. Extensive cellular characterization, including distal lung immunofluorescence and cytospin staining, confirmed that GRAMD2+ AT1 cells are highly enriched for green fluoresecent protein (GFP). Interestingly, Gramd2CreERT2 GFP+ cells were able to form colonies in organoid co-culture with Mlg fibroblasts. Temporal scRNAseq revealed that Gramd2+ AT1 cells transition through numerous intermediate lung epithelial cell states including basal, secretory and AT2 cell in organoids while acquiring proliferative capacity. Our results indicate that Gramd2+ AT1 cells are highly plastic suggesting they may contribute to alveolar regeneration.
2023-10-04 | GSE235217 | GEO
Project description:Cardiac organoid model of human myocardial infarction
| PRJNA454314 | ENA