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Development of novel in vitro human alveolar epithelial cell models to study distal lung biology and disease [scRNA-seq]

ABSTRACT: Development of novel in vitro human alveolar epithelial cell models to study distal lung biology and disease [scRNA-seq]

PROVIDER: PRJNA691041 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13397562_1.fastq.gz	Fastqsanger.gz
	SRR13397562_2.fastq.gz	Fastqsanger.gz
	SRR13397563_1.fastq.gz	Fastqsanger.gz
	SRR13397563_2.fastq.gz	Fastqsanger.gz
	SRR13397564_1.fastq.gz	Fastqsanger.gz

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Development of novel in vitro human alveolar epithelial cell models to study distal lung biology and disease.

Project description:Development of novel in vitro human alveolar epithelial cell models to study distal lung biology and disease.

| PRJNA691039 | ENA

Development of novel in vitro human alveolar epithelial cell models to study distal lung biology and disease [scRNA-seq]

Project description:To address the need for human alveolar epithelial cell (AEC)-derived lines to more suitably model distal lung diseases, we have generated and characterized novel immortalized cell lines derived from human AECs. We used a combination of the ROCK inhibitor, Y-27632, and lentiviral transduction of SV40 Large T antigen of previously cryopreserved isolated human alveolar epithelial type 2 (AT2) cells to generate immortalized AECs. These AEC lines proliferate well on standard tissue culture dishes forming an epithelial monolayer and express lung progenitor markers SOX9 and SOX2. When grown in 3D culture with lung fibroblasts, the cells form NKX2-1+ organoids expressing more mature alveolar lung markers, AQP5 and GPRC5A. Single cell RNA-sequencing of one AEC line comparing cells in 2D versus 3D revealed increased cellular heterogeneity and an induction of cytokine and lipoprotein signaling in 3D culture, reflecting interactions with the microenvironment during organoid formation. Taken together, these data show our novel progenitor-like AEC lines retain a genetic and structural memory of their alveolar cell lineage despite long-term expansion, providing a valuable new system to model the distal lung in vitro.

2022-01-10 | GSE164514 | GEO

Development of novel in vitro human alveolar epithelial cell models to study distal lung biology and disease [bulk RNA-seq]

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Development of novel in vitro human alveolar epithelial cell models to study distal lung biology and disease [bulk RNA-seq]

Project description:Development of novel in vitro human alveolar epithelial cell models to study distal lung biology and disease [bulk RNA-seq]

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Single-cell RNA Sequencing of Murine Lungs to Compare Two Different Models of Alveolar Simplification

Project description:Neonatal hyperoxia exposure causes alveolar simplification in mice and has been employed as a model to study bronchopulomonary dysplasia, or chronic lung disease of prematurity. Loss of epithelial TGF-beta signaling has also been shown to cause alveolar simplification in mouse models of lung development. We used single cell RNA sequencing (scRNA-seq) to analyze both of these models of lung injury to identify shared molecular and cellular mechanisms that contribute to pathogenic alveolar simplification.

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Mouse Models of Alveolar/Embryonal Rhabdomyosarcoma & Spindle Cell Sarcomas

Project description:A series of conditional mouse models of embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma and spindle cell sarcoma were generated and validated for relavence to corresponding human cancers. Conditional mouse models of embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma and spindle cell sarcoma were created by activation or deletion of Pax3:Fkhr, p53, Ptch1 or Rb1 genes.

2011-02-17 | E-GEOD-22520 | biostudies-arrayexpress

Development of human alveolar epithelial cell models to study distal lung biology and disease.

Project description:Many acute and chronic diseases affect the distal lung alveoli. Alveolar epithelial cell (AEC) lines are needed to better model these diseases. We used de-identified human remnant transplant lungs to develop a method to establish AEC lines. The lines grow well in 2-dimensional (2D) culture as epithelial monolayers expressing lung progenitor markers. In 3-dimensional (3D) culture with fibroblasts, Matrigel, and specific media conditions, the cells form alveolar-like organoids expressing mature AEC markers including aquaporin 5 (AQP5), G-protein-coupled receptor class C group 5 member A (GPRC5A), and surface marker HTII280. Single-cell RNA sequencing of an AEC line in 2D versus 3D culture revealed increased cellular heterogeneity and induction of cytokine and lipoprotein signaling in 3D organoids. Our approach yields lung progenitor lines that retain the ability to differentiate along the alveolar cell lineage despite long-term expansion and provides a valuable system to model and study the distal lung in vitro.

| S-EPMC8829779 | biostudies-literature

Development of novel in vitro human alveolar epithelial cell models to study distal lung biology and disease.

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-01-10 | GSE164515 | GEO

Mouse Models of Alveolar/Embryonal Rhabdomyosarcoma & Spindle Cell Sarcomas

2011-02-17 | GSE22520 | GEO

Interleukin-11 causes alveolar type 2 cell dysfunction and prevents alveolar regeneration [scRNA-Seq]

Project description:Following lung injury, alveolar regeneration is characterized by the transformation of alveolar type 2 (AT2) cells, via a transitional KRT8+ state, into alveolar type 1 (AT1) cells. In lung disease, dysfunctional intermediate cells accumulate, AT2 and AT1 cells are diminished and fibrosis occurs. Using single cell RNA sequencing (scRNA-seq) datasets of human interstitial lung disease, we found that Interleukin-11 (IL11) is specifically expressed in aberrant KRT8 expressing KRT5-/KRT17+ epithelial cells and basaloid cells. Stimulation of AT2 cells and distal airway epithelial cells with IL11 or TGFβ1 caused epithelial-to-mesenchymal transition (EMT), induced extracellular matrix (ECM) production, increased KRT8 expression and stalled AT2-to-AT1 differentiation, with TGFβ1 effects being partially IL11 dependent. In bleomycin injured mouse lung, IL11 was increased in AT2-derived Krt8+ transitional cells and deletion of Il11ra1 in AT2 lineage cells prevented the accumulation of Krt8+ transitional cells, enhanced AT1 differentiation and promoted alveolar regeneration, which was replicated in therapeutic studies using anti-IL11 antibodies. scRNA-seq analysis of lung epithelial cells from mice with deletion of Il11ra1 in AT2 lineage cells further identified the importance of IL11 signaling for the potentiation and polarization of a disease-causing, ECM producing KRT8+ transitional cells that contributes to pathological lung remodeling. Overall, our data show that IL11 maintains damaged AT2 cells in a transitional state, impairs reparative AT1 differentiation and impairs endogenous alveolar regeneration to cause fibrotic lung disease.

2024-08-12 | GSE261793 | GEO

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