Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Age-Dependent Transcriptomic and DNA Methylation Alterations in Fibroblasts During Resolving and Persistent Lung Fibrosis

ABSTRACT: The activation of fibroblasts in response to lung injury is an adaptive and necessary process for physiological repair, but their persistent activation can lead to excessive scarring and impaired fibrosis resolution. Although the model of bleomycin-induced lung fibrosis in young adult mice is often criticized because fibrosis spontaneously resolves, comparisons of this model with aged mice, in which fibrosis persists, can provide important insights into the genes and pathways that modulate persistent vs resolving fibrosis. Changes in DNA methylation are a prominent feature of aging and pulmonary fibrosis. Here, we explore the differential expression and DNA methylation patterns that occur in lung fibroblasts of young and aged mice during persistent and resolving fibrosis.

ORGANISM(S): Mus musculus

PROVIDER: GSE324715 | GEO | 2026/06/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Investigating the role of aging and lung fibrosis in Endothelial Cells with ATAC sequencing

2022-05-09 | GSE177055 | GEO

Investigating the role of aging and lung fibrosis in Endothelial Cells with RNA sequencing

Project description:In order to elucidate the contribute of the pulmonary vasculature to lung fibrosis, we injured young and aged mice with bleomycine, to create a model of resolving versus persistent lung fibrosis. The animals were sacrificed 30 days after the injury (time point in which we observed a divergent resolving vs persistent lung fibrosis in young vs aged mice). We found that lung fibrosis resolution in young mice was accompained by the activation of transcriptional programs promoting vascular repair and lung fibrosis resolution. Lung endothelial cells from aged mice after injury failed to activate these programs, leading to dysrepair and progressive fibrosis.

2021-09-30 | GSE181508 | GEO

Comparative transcriptional analysis of lung fibroblasts from young and aged mice identifies PIM1/NFATc1 axis as a driver of persistent fibrosis

Project description:Idiopathic pulmonary fibrosis (IPF) is an aging-associated disease characterized by the accumulation of myofibroblasts leading to the progressive scarring of the lung. To identify transcriptional gene programs driving persistent fibrosis in aged lungs, we performed a comparative RNA-seq analysis of fibroblasts freshly isolated from young and aged mouse lungs 30 days post-bleomycin injury. We discovered that lung fibroblasts isolated from young animals at this time point post-injury were transcriptionally similar to those isolated from uninjured mice. In contrast, aged lung fibroblasts isolated at the same time point exhibited a sustained pro-fibrotic state characterized by the elevated expression of genes implicated in inflammation, extracellular matrix remodeling, and cell survival. We identified the protein kinase pro-viral integration site of Moloney murine leukemia virus 1 (PIM1) and its direct target Nuclear Factor of Activated T Cells-1 (NFATc1) as putative drivers of the sustained profibrotic gene signatures observed in aged lung fibroblasts post-injury. PIM1 and NFATc1 transcripts were highly enriched in a pathogenic fibroblast population recently discovered in IPF lungs, and their protein expression was detected in fibroblastic foci. Overexpression of PIM1 in normal human lung fibroblasts potentiated their fibrogenic activation and this effect was dependent on NFATc1. Pharmacological inhibition of PIM1 in IPF-derived lung fibroblasts attenuated their activation and sensitized them to apoptotic stimuli. Finally, inhibition of PIM1 strongly reduced the expression of ECM remodeling and pro-survival genes and blocked the secretion of collagen in IPF lung explants ex vivo. Targeting PIM1/NFATc1 axis in pathogenic lung fibroblasts may represent a therapeutic strategy to limit their activation and promote fibrosis resolution in IPF.

2022-01-01 | GSE191208 | GEO

Lung injury-induced endothelial cell states persist in aging-associated non-resolving fibrosis

Project description:The capacity of lung tissue to heal without scarring deteriorates with aging. The pulmonary vasculature has emerged as a central regulator of lung repair, and aging-associated endothelial cell dysfunction has been associated with defective lung response to injury and sustained fibrosis. To shed light into aging-associated cellular and transcriptional responses of lung endothelial cells during lung fibrogenesis, we carried out a single cell RNA-seq analysis of bleomycin-treated young (2 months) and aged (72 months) lungs during the early phase of fibrosis resolution (30 days post bleomycin). This analysis revealed that lung injury was associated with the appearance of distinct populations of endothelial cells that exhibit “activated” transcriptional states, originating from virtually all vascular beds. Activated endothelial cells deriving from venous and capillary beds were the most represented in aged compared to young lungs. Longitudinal single-cell analysis together with lineage tracing revealed that activated endothelial cells appeared transiently during the peak of collagen production in young lungs and disappeared during the resolution phase. Conversely, activated endothelial cell states persisted in aged lungs around fibrotic areas, indicating a failure of the aged vascular tissue to return to quiescence. We provide evidence that an axis between YAP and TrkB signaling acts as a node that directs injury-induced capillary endothelial cell activation in vivo and lung capillary morphogenesis ex vivo. Together, these data provide insights into the aging-related dynamics of lung endothelial cells in response to injury.

2024-06-04 | GSE264151 | GEO

Lung injury-induced endothelial cell states persist in aging-associated non-resolving fibrosis II

2024-06-04 | GSE264162 | GEO

Bleomycin model of fibrosis and resolution phase in old and young mice

Project description:Bleomycin-induced pulmonary fibrosis in mice mimics major hallmarks of idiopathic pulmonary fibrosis, yet in this model it spontaneously resolves over time. We studied molecular mechanisms of fibrosis resolution and lung repair, focusing on transcriptional and proteomic signatures and the effect of aging. Young (3 months) and old (21 months) mice were treated with Bleomycin or with control saline solution and analyzed transcript and protein expression over 8 weeks (Day 0, 14, 21, 28, 35, 42, 49, 56).

2023-08-09 | PXD041050 | Pride

Bleomycin model of fibrosis and resolution phase in old and young mice

2024-09-10 | PXD040530 | Pride

Emergence of inflammatory fibroblasts with aging in Hermansky-Pudlak syndrome associated pulmonary fibrosis

Project description:The longitudinal cellular interactions that drive pulmonary fibrosis are not well understood. To investigate the disease underpinnings associated with fibrosis onset and progression, we generated a scRNAseq atlas of lungs from young and aged mouse models of multiple subtypes of Hermansky-Pudlak syndrome (HPS), a collection of rare autosomal recessive diseases associated with albinism, platelet dysfunction, and pulmonary fibrosis. We identified an age-dependent increase in SAA3+ inflammatory lung fibroblasts in HPS mice, including in double-mutant HPS1-2 mice which develop spontaneous fibrosis. HPS1 fibroblasts showed increased expression of IL-1R1, whereas alveolar type II epithelial cells from HPS2 mice induced the inflammatory gene signature in co-cultured fibroblasts. scRNAseq of lung tissue from three HPS1 patients similarly showed the presence of inflammatory fibroblasts and increased IL1R1 expression on fibroblasts. These data posit complex interactions between dysfunctional epithelial cells, inflammatory fibroblasts, and recruited immune cells, suggesting potential opportunities for mitigation of the fibrotic cascade.

2025-02-07 | GSE272904 | GEO

Spatiotemporal resolving Crohn's disease fibrosis

Project description:Spatiotemporal resolving Crohn's disease fibrosis

| PRJNA1162010 | ENA

Comparative transcriptional analysis of lung fibroblasts from young and aged mice identifies PIM1/NFATc1 axis as a driver of persistent fibrosis

Project description:Comparative transcriptional analysis of lung fibroblasts from young and aged mice identifies PIM1/NFATc1 axis as a driver of persistent fibrosis

| PRJNA790454 | ENA

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data