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Pulmonary fibrosis distal airway epithelia are dynamically and structurally dysfunctional

ABSTRACT: Pulmonary fibrosis distal airway epithelia are dynamically and structurally dysfunctional

PROVIDER: PRJNA734567 | ENA |

REPOSITORIES: ENA

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Pulmonary fibrosis distal airway epithelia are dynamically and structurally dysfunctional

Project description:To identify genes regulating the jamming transition in healthy distal airway epithelia compared to the dysregulated state in idiopathic pulmonary fibrosis epithelia (IPF) we analyzed RNA from three (3) healthy and four (4) IPF patient cells grown at air-liquid-interface (ALI). This bulk analysis of 3 timepointes (days 4, 8, and 14 of ALI) spanning the jamming transition revealed an enrichment for ERBB- and YAP-related genes.

2021-07-01 | GSE176001 | GEO

Pulmonary fibrosis distal airway epithelia are dynamically and structurally dysfunctional.

Project description:The airway epithelium serves as the interface between the host and external environment. In many chronic lung diseases, the airway is the site of substantial remodeling after injury. While, idiopathic pulmonary fibrosis (IPF) has traditionally been considered a disease of the alveolus and lung matrix, the dominant environmental (cigarette smoking) and genetic (gain of function MUC5B promoter variant) risk factor primarily affect the distal airway epithelium. Moreover, airway-specific pathogenic features of IPF include bronchiolization of the distal airspace with abnormal airway cell-types and honeycomb cystic terminal airway-like structures with concurrent loss of terminal bronchioles in regions of minimal fibrosis. However, the pathogenic role of the airway epithelium in IPF is unknown. Combining biophysical, genetic, and signaling analyses of primary airway epithelial cells, we demonstrate that healthy and IPF airway epithelia are biophysically distinct, identifying pathologic activation of the ERBB-YAP axis as a specific and modifiable driver of prolongation of the unjammed-to-jammed transition in IPF epithelia. Furthermore, we demonstrate that this biophysical state and signaling axis correlates with epithelial-driven activation of the underlying mesenchyme. Our data illustrate the active mechanisms regulating airway epithelial-driven fibrosis and identify targets to modulate disease progression.

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Dysfunctional CD8+ T cells form a proliferative, dynamically regulated compartment within human melanoma [scRNA-seq]

Project description:Tumor immune cell compositions play a major role in response to immunotherapy but the heterogeneity and dynamics of immune infiltrates in human cancer lesions remain poorly characterized. Here we identify conserved intratumoral CD4 and CD8 T cell behaviors in scRNA-seq data from 25 melanoma patients. We discover a large population of CD8 T cells showing continuous progression from an early effector “transitional” into a dysfunctional T cell state. CD8 T cells that express a complete cytotoxic gene set are rare, and TCR sharing data suggest their independence from the transitional and dysfunctional cell states. Notably, we demonstrate that dysfunctional T cells are the major intratumoral proliferating immune cell compartment and that the intensity of the dysfunctional signature is associated with tumor-reactivity. Our data demonstrate that CD8 T cells previously defined as exhausted, are in fact a highly proliferating, clonal and dynamically differentiating cell population within the human tumor microenvironment.

2018-12-27 | GSE123139 | GEO

Dysfunctional CD8+ T cells form a proliferative, dynamically regulated compartment within human melanoma [scRNA-seq]

Project description:Dysfunctional CD8+ T cells form a proliferative, dynamically regulated compartment within human melanoma [scRNA-seq]

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Expression data from human airway epithelia exposed to IL13

Project description:IL13 exposure results in a distinct gene expression profile in human airway epithelia. We investigated whether this expression profile can be used to identify compounds able to block goblet cell metaplasia We used microarrays to determine transcriptional changes in cultures of primary human airway epithelia grown at the air-liquid interface after exposure to 20 ng/mL recombinant human IL13

2017-11-14 | GSE106812 | GEO

Single-cell RNA sequencing of human airway epithelia infected with measles virus (MeV)

Project description:The goal of this study was to compare cell composition, gene expression, and infectivity of different cell types in human airway epithelia following exposure to measles virus. Samples included control epithelia exposed to a mock infection and measles-virus-exposed epithelia that were sorted according to detection of green fluorescent protein (GFP) prior to library preparation and sequencing.

2021-08-06 | GSE168775 | GEO

Single cell RNA sequencing of healthy human airway epithelia

Project description:The goal of this study was to compare cell composition and gene expression of different cell types in healthy primary human airway epithelia cultured at the air-liquid interface

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Repair of airway epithelia requires metabolic rewiring towards fatty acid oxidation

Project description:Repair of airway epithelia requires metabolic rewiring towards fatty acid oxidation

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Identification of protein interactors of SPAG1 in human airway epithelia

Project description:Dysfunctional motile cilia result in primary ciliary dyskinesia (PCD), a genetically heterogeneous disorder characterized by chronic oto-sino-pulmonary disease, infertility, and laterality defects. Mutations in dynein axonemal assembly factors (DNAAF), that facilitate the assembly of dynein arms in the cytoplasm before transport into the cilium, cause PCD. Sperm-associated antigen 1 (SPAG1) is a DNAAF; however, SPAG1’s precise role in dynein assembly is unknown. Here, we identify a novel 60 kDa SPAG1 isoform that can partially compensate for the absence of full-length SPAG1 to assemble normal outer dynein arms, leading to phenotypic variability in PCD subjects with SPAG1 mutations. Our data shows that SPAG1 interacts with DNAAF, dynein chains, and components of the R2TP complex, and SPAG1 is necessary for axonemal dynein arm assembly by facilitating the folding and/or binding of the dynein heavy chains to the intermediate chain complex.

2022-03-20 | PXD032349 | Pride

Expression data from human airway epithelia exposed to IL13

Project description:Expression data from human airway epithelia exposed to IL13

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