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Senescence rather than apoptosis of alveolar progenitor cells drives pulmonary fibrosis

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE132915 | GEO | 2020/06/30

REPOSITORIES: GEO

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Senescence rather than apoptosis of alveolar progenitor cells drives pulmonary fibrosis (human)

Project description:Idiopathic pulmonary fibrosis (IPF) is a fatal form of interstitial lung disease associated with progressive scarring of lung tissue and declining pulmonary function in aging individuals. Here we employ data mining and single cell RNA sequencing (scRNAseq) to define candidate drivers of AT2 senescence in IPF lung tissue. We show that AT2 cells isolated from IPF lung tissue exhibit characteristic features of cellular senescence and reduced abundance of Sin3a, critical determinant of endodermal progenitor cell maintenance in the developing lung. Conditional loss of Sin3a within AT2 cells of the adult mouse lung activated a program of p53-dependent cellular senescence and AT2 cell depletion, leading to progressive pulmonary fibrosis. In contrast, ablation of AT2 cells through conditional activation of a DTA toxin gene led to transient fibrosis that resolved over time, suggesting that senescence of AT2 cells was a critical driver of progressive fibrosis. Activation of b6 integrin was observed within a subset of AT2 cells with Sin3a loss-of-function that localized to the advancing margin of advancing fibroproliferative lesions. Systemic inhibition of TGF signaling or delivery of senolytic drugs prevented lung fibrosis in Sin3a loss-of-function mice. Our findings establish a novel mouse model that recapitulates key pathological features of human IPA and show that p53-dependent senescence is a proximal regulator of TGF induction and progressive pulmonary fibrosis.

2020-06-30 | GSE132914 | GEO

Senescence rather than apoptosis of alveolar progenitor cells drives pulmonary fibrosis (mouse scRNAseq)

2020-06-30 | GSE132910 | GEO

Senescence rather than apoptosis of alveolar progenitor cells drives pulmonary fibrosis (mouse_bulk RNAseq)

Project description:bulk RNAseq comparison of global transcription profiles of mouse lung AT2 Sin3a-LOF at different time points, evalute AT2 cellular senescecne contribution to lung fibrosis.

2020-06-30 | GSE132909 | GEO

Senescence rather than apoptosis of alveolar progenitor cells drives pulmonary fibrosis (mouse bulk AT2)

Project description:bulk RNAseq of AT2 cells transcriptome changes comparing Sin3aLOF with control two weeks after tamoxifen treatment

2020-06-30 | GSE132908 | GEO

Senescence rather than apoptosis of alveolar progenitor cells drives pulmonary fibrosis

Project description:Senescence rather than apoptosis of alveolar progenitor cells drives pulmonary fibrosis

| PRJNA549450 | ENA

Senescence rather than apoptosis of alveolar progenitor cells drives pulmonary fibrosis (human)

Project description:Senescence rather than apoptosis of alveolar progenitor cells drives pulmonary fibrosis (human)

| PRJNA549454 | ENA

Senescence rather than apoptosis of alveolar progenitor cells drives pulmonary fibrosis (mouse scRNAseq)

Project description:Senescence rather than apoptosis of alveolar progenitor cells drives pulmonary fibrosis (mouse scRNAseq)

| PRJNA549452 | ENA

Senescence rather than apoptosis of alveolar progenitor cells drives pulmonary fibrosis (mouse_bulk RNAseq)

Project description:Senescence rather than apoptosis of alveolar progenitor cells drives pulmonary fibrosis (mouse_bulk RNAseq)

| PRJNA549453 | ENA

Senescence rather than apoptosis of alveolar progenitor cells drives pulmonary fibrosis (mouse bulk AT2)

Project description:Senescence rather than apoptosis of alveolar progenitor cells drives pulmonary fibrosis (mouse bulk AT2)

| PRJNA549446 | ENA

LKB1 inhibition in alveolar epithelial cells induces fibroblast activation in pulmonary fibrosis

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

2023-08-09 | GSE205970 | GEO

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