Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Aberrant differentiation of epithelial progenitors is accompanied by a hypoxic microenvironment in the paraquat-injured human lung

ABSTRACT: Paraquat is a toxic herbicide that can cause severe lung injury, leading to alveolar epithelial cell death, subsequent lung fibrosis and respiratory failure. Understanding the repair process following paraquat injury is critical for developing effective therapeutic strategies to treat paraquat-poisoned patients. However, the lung repair program in paraquat-injured lungs is currently unknown. In this study, we analyzed lung parenchyma samples from an 18-year-old female patient who had ingested paraquat and subsequently underwent a double-lung transplantation on the 34th day after poisoning. By the combination of single cell RNA sequencing analysis and immunostaining analysis, we reveal that the airway stem/progenitor cells and AT2 cells in the paraquat-injured lung exhibit a significantly reduced capacity to regenerate alveolar epithelium epithelial in the paraquat-injured lung. The hypoxic microenvironment may contribute to this aberrant repair program by activating the NOTCH signaling pathway, ultimately leading to an irreversible loss of gas-exchange units and an exacerbated lung tissue damage.

ORGANISM(S): Homo sapiens

PROVIDER: GSE231647 | GEO | 2023/09/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Transcriptome of Paraquat-induced Pulmonary Fibrosis

Project description:PURPOSE: Pulmonary fibrosis (PF) is a pathological state presenting at the progressive stage of heterogeneous interstitial lung disease (ILD). The molecular mechanisms are incompletely understood. We built a mouse model of lung fibrosis induced by paraquat. Using transcriptome analysis, we identified differentially expressed proteins (DEGs) and provided further functional analysis. METHODS: We built a mouse model of lung fibrosis through intratracheal instillation of paraquat. After instillation, mice were kept for 7 and 28 days, respectively. we performed time-series RNA sequencing (RNA-Seq) on the lung samples from paraquat treated mice and saline control. The DEGs were verified by qPCR. RESULTS: The transcriptome data found a total of 1345 of differentially expressed genes (DEGs) up-regulated and 844 DEGs down-regulated significantly in paraquat group on day 7. There were 511 DEGs up-regulated and 179 DEGs down-regulated remarkably on day 28 after PQ instillation (Fold Change ≥2 and Q value ≤0.001). We verified 6 significantly changed genes by qPCR, proving the accuracy of RNA-seq. CONCLUTION: Our transcriptomic study assigns genes for fibrogenesis and reveals their dynamic changes from lung injury to repair, providing new insights for the and development of biomarkers and treatment in fibrotic diseases.

2024-04-01 | GSE171625 | GEO

Intersectional genetic tracing reveals the origin of alveolar stem cells during lung repair and regeneration

Project description:Alveolar type 2 (AT2) cells are stem cells of the alveolar epithelia. Previous genetic lineage tracing studies reported multiple cellular origins for AT2 cells after injury. However, conventional lineage tracing based on Cre-loxP has the limitation of non-specific labeling. Thus, the exact contribution of various epithelial cells to the pools of AT2 cells under different conditions remains unclear. Here, we used dual recombinases-mediated intersectional genetic lineage tracing to investigate the cellular origins of AT2 cells during lung homeostasis, injury and repair. In contrast to previous studies, we found AT1 cells were terminally differentiated cells and did not contribute to AT2 cells after lung injury and repair. Distinctive, but simultaneous, labeling of club cells, bronchioalveolar stem cells (BASCs), and AT2 cells revealed the exact contribution of each to AT2 cells after lung injury. Moreover, we found that club cells have the potential to rebuild virtually all alveoli in some severely injured lung regions. Mechanistically, Notch signaling promotes a BASCs-to-AT2 cell transition, but it inhibits club cell-to-AT2 cell conversion during lung repair. This intersectional genetic lineage tracing strategy with enhanced precision allowed us to elucidate the physiological role of AT1, club, BASCs, and AT2 cells to alveolar regeneration after injury.

2024-01-06 | GSE252588 | GEO

Gene network analysis of interstitial macrophages after treatment with induced pluripotent stem cells secretome (iPSC-cm) in the bleomycin injured rat lung

Project description:Idiopathic pulmonary fibrosis (IPF) is a complex disease involving various cell types. Macrophages are essential in maintenance of physiological homeostasis, wound repair and fibrosis in the lung. Macrophages play a crucial role in repair and remodeling by altering their phenotype and secretory pattern in response to injury. The secretome of induced pluripotent stem cells (iPSC-cm) attenuates injury and fibrosis in bleomycin injured rat lungs. In the current study, we evaluate the effect of iPSC-cm on interstitial macrophage gene expression and phenotype in bleomycin injured rat lungs in vivo. Â iPSC-cm was intratracheally instilled 7 days after bleomycin induced lung injury and assessed 7 days later and single cell isolation was performed. Macrophages were FACS sorted and microarray analysis was performed. We characterized changes in the rat lung interstitial macrophages using transcriptional profiling.

2017-03-20 | E-MTAB-5619 | biostudies-arrayexpress

Airway-derived p63+ facultative progenitors contribute to alveolar regeneration after lung injury.

Project description:Lung injury activates potential stem cells or progenitors for alveolar repair and regeneration. However, the activation program and source of injury-induced facultative progenitors remain incompletely known. Here, we find that lung injury induces emergence of p63-expressing progenitors, which rapidly proliferate and differentiate into alveolar type-1 (AT1) and type-2 (AT2) cells. scRNA-seq analysis uncovers that a subset of p63+ progenitors exhibit two distinct parallele transient stages before differentiation into mature AT1 and AT2 cells, respectively. Dual recombinases-mediated sequential genetic tracing reveals that facultative p63+ progenitors originate from the distal airway secretory cells and subsequently regenerate alveoli. Functioanlly, secretory cell-specific knockout of p63 significantly impairs their contribution to alveolar epithelium during lung regeneration. Our study identified secretory cell-derived facultative p63+ progenitors that contribute to alveolar regeneration, indicating a potential therapeutic target for lung treatment after injuires.

2023-02-20 | GSE225187 | GEO

Bj Paraquat

Project description:This SuperSeries is composed of the following subset Series: GSE26236: Bj Paraquat fulminant shock vs. non-treatment GSE26252: Bj Paraquat prolonged exposure vs. non-treatment Refer to individual Series

2011-05-15 | E-GEOD-26531 | biostudies-arrayexpress

scRNA-seq of Human Alveolar Type 2 Cell Organoids

Project description:Alveolar type 2 (AT2) cells function as stem cells in the adult lung and aid in injury-repair. The current study aimed to understand the signaling events that control differentiation of this therapeutically relevant cell type during human development through differentiation of lung progenitor organoids to AT2 cells and benchmarking against primary AT2 organoids.

2023-06-15 | E-MTAB-12960 | biostudies-arrayexpress

RNA-Sequencing from ventral mid brain and striatum of paraquat, pyridaben and paraquat+maneb mice models of Parkinson's disease.

Project description:We report RNA-sequencing from ventral mid brain and striatum from paraquat, pyridaben and paraquat+maneb mice models of Parkinson's disease. We observed several differentially expressed genes upon pesticide exposure which we analyzed by pathway analysis.

2012-09-04 | GSE36232 | GEO

p53 governs an alveolar type 1 differentiation program in lung cancer suppression [10x_multiome_ATAC]

Project description:Lung cancer is the leading cause of cancer deaths worldwide. TP53 tumor suppressor gene mutations occur in 50% of lung adenocarcinomas (LUADs) and are linked to poor prognosis, but how p53 suppresses LUAD development remains enigmatic. We show here that p53 suppresses LUAD by governing cell state, by promoting alveolar type 1 (AT1) differentiation. Using mice expressing oncogenic Kras and null, wild-type, or hypermorphic p53 alleles in alveolar type 2 (AT2) cells, we observed graded effects of p53 on LUAD initiation and progression. RNA-sequencing and ATAC-sequencing of LUAD cells uncovered a p53-induced AT1 differentiation program during tumor suppression in vivo through direct DNA binding, chromatin remodeling, and AT1 gene induction. Single-cell transcriptomics analyses revealed that during LUAD evolution, p53 promotes AT1 differentiation through action in a transitional cell state analogous to a transient intermediary seen during AT2-to-AT1 differentiation in alveolar injury repair. Notably, p53 inactivation resulted in the inappropriate persistence of these transitional cancer cells accompanied by upregulated growth signaling and divergence from lung lineage identity, characteristics associated with LUAD progression. Analysis of p53wt and p53-null mice showed that p53 also directs alveolar regeneration after injury, by regulating AT2 self-renewal and promoting transitional cell differentiation into AT1 cells. Collectively, these findings illuminate mechanisms of p53-mediated LUAD suppression, in which p53 governs alveolar differentiation, and suggest that tumor suppression reflects a fundamental role of p53 in orchestrating tissue repair after injury.

2023-05-04 | GSE231671 | GEO

p53 governs an alveolar type 1 differentiation program in lung cancer suppression [in_vivo_RNA_seq]

2023-05-04 | GSE231679 | GEO

p53 governs an alveolar type 1 differentiation program in lung cancer suppression [in_vitro_RNA_seq]

2023-05-04 | GSE231678 | GEO