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: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:Lung cancer is the leading cause of cancer-related death worldwide. Lung adenocarcinoma (LUAD), the most common histological subtype, accounts for 40% of all cases. While existing genetically engineered mouse models (GEMMs) recapitulate the histological progression and transcriptional evolution of human LUAD, they are time-consuming and technically demanding. In contrast, cell line transplant models are fast and flexible, but these models fail to capture the full spectrum of disease progression. Organoid technologies provide a means to create next-generation cancer models that integrate the most advantageous features of autochthonous and transplant-based systems. However, robust and faithful LUAD organoid platforms are currently lacking. Here, we describe optimized conditions to continuously expand murine alveolar type 2 cells (AT2), a prominent cell-of-origin for LUAD, in organoid culture. These organoids display canonical features of AT2 cells, including marker gene expression, the presence of lamellar bodies, and an ability to differentiate into the AT1 lineage. We used this system to develop flexible and versatile immunocompetent organoid-based models of KRAS, BRAF, and ALK-mutant LUAD. Notably, organoid-based tumors display extensive burden and complete penetrance, and are histopathologically indistinguishable from their autochthonous counterparts. Altogether, this organoid platform is a powerful, versatile new model system to study LUAD.
2023-01-02 | GSE213971 | GEO
Project description:Cardiac organoid model of human myocardial infarction
| PRJNA454314 | ENA
Project description:Lung cancer is the leading cause of cancer-related death worldwide. Lung adenocarcinoma (LUAD), the most common histological subtype, accounts for 40% of all cases. While existing genetically engineered mouse models (GEMMs) recapitulate the histological progression and transcriptional evolution of human LUAD, they are time-consuming and technically demanding. In contrast, cell line transplant models are fast and flexible, but these models fail to capture the full spectrum of disease progression. Organoid technologies provide a means to create next-generation cancer models that integrate the most advantageous features of autochthonous and transplant-based systems. However, robust and faithful LUAD organoid platforms are currently lacking. Here, we describe optimized conditions to continuously expand murine alveolar type 2 cells (AT2), a prominent cell-of-origin for LUAD, in organoid culture. These organoids display canonical features of AT2 cells, including marker gene expression, the presence of lamellar bodies, and an ability to differentiate into the AT1 lineage. We used this system to develop flexible and versatile immunocompetent organoid-based models of KRAS, BRAF, and ALK-mutant LUAD. Notably, organoid-based tumors display extensive burden and complete penetrance, and are histopathologically indistinguishable from their autochthonous counterparts. Altogether, this organoid platform is a powerful, versatile new model system to study LUAD.
2023-01-02 | GSE213974 | GEO
Project description:Cardiac organoid model of human myocardial infarction (batch2)
| PRJNA473541 | ENA
Project description:Our data show that Wnt and FGF signalling, and the downstream transcription factors NKX2.1 and TFAP2C, promote human alveolar or airway fate respectively. Moreover, we have functionally validated cell-cell interactions in human lung alveolar patterning. We show that Wnt signalling from differentiating fibroblasts promotes alveolar type 2 cell identity, whereas myofibroblasts secrete the Wnt inhibitor, NOTUM, providing spatial patterning. Our organoid system recapitulates key aspects of human lung development allowing mechanistic experiments to determine the underpinning molecular regulation.
2022-02-28 | E-MTAB-11435 | biostudies-arrayexpress
Project description:Patient derived organoids (PDOs) have been established as a 3D culture model which closely recapitulates the in vivo tumor biology. However, one limitation of this culture model is the lack of tumor microenvironment which has a significant role in tumor progression and drug response. To address this, we established and molecularly characterized a novel 3D co-culture model of colorectal cancer (CRC) based on PDOs and patient matched fibroblasts. Both normal and cancer associated fibroblasts, NFs and CAFs respectively, were able to support organoid growth without addition of niche factors to the media. Additionally, co-cultures showed closer resemblance to primary patient material than organoid mono-cultures as evaluated by histology. Finally, RNA gene expression signatures of tumor cells and fibroblasts isolated from mono- or co-cultures demonstrated that co-cultures support greater cell type heterogeneity. In this proteomics dataset we compared pairs of NFs and CAFs derived from five patients. Collectively, we present a newly established human derived organoid-fibroblast model which, closely recapitulates in vivo tumor heterogeneity and involves the tumor microenvironment.
2023-03-14 | PXD032047 | Pride
Project description:Atosiban harness hepatocellular carcinoma progression in human organoid model
| PRJNA1106421 | ENA
Project description:A cultured sensorimotor organoid model forms human neuromuscular junctions
| PRJNA732479 | ENA