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

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

ORGANISM(S): Mus musculus

PROVIDER: GSE132908 | 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_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 scRNAseq)

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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

Senescence rather than apoptosis of alveolar progenitor cells drives pulmonary fibrosis

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

2020-06-30 | GSE132915 | GEO

The single cell RNA seq of pulmonary alveolar type II (AT2) cells

Project description:The pulmonary alveolar epithelium mainly composed of two types of epithelial cells: alveolar type I (AT1) and type II (AT2) cells. AT2 cells are the alveolar stem cells, and can differentiate into AT1 cells post-pneumonectomy (PNX). Here, we found that, compared with control mice (Sftpc-CreER; Cdc42flox/+; Rosa26-mTmG) at post-PNX day 21, Cdc42 AT2 null mice (Sftpc-CreER; Cdc42flox/-; Rosa26-mTmG) at post-PNX day 21 undergone fibrotic change. By using 10X genomics “Chromium Single Cell” technology, we performed single-cell RNA-seq analyses of AT2 cells of sham treated control mice (C0), AT2 cells of control mice at post PNX day 21 (C21) , AT2 cells of sham treated Cdc42 AT2 null mice (N0), and AT2 cells of Cdc42 AT2 null mice at post PNX day 21 (N21). The study identified a specific gene signature in AT2 cells of Cdc42 AT2 null mice at post PNX day 21 which is related to the fibrosis phenotype of Cdc42 AT2 null mice.

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Senescence rather than apoptosis of alveolar progenitor cells drives pulmonary fibrosis

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

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Gene expression profile at single cell level of total alveolar type II (AT2) cells and CD44hi AT2 cells

Project description:AT2 cells are the resident progenitor cells in alveoli, capable of self-proliferation and differentiation into alveolar type I cells during homeostatic maintenance and tissue regeneration. The AT2 cell population is heterogenous. We identified a small subpopulation of AT2 cells that express high levels of CD44 (CD44hi) and display progenitor functions during alveoli homeostasis. To further analyze the heterogeneity of the AT2 cell population and characterize CD44hi AT2 cells, we performed single cell RNA-seq on the total AT2 cell population and CD44hi AT2 cells.

2024-05-24 | GSE202226 | GEO

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

Modeling of Aberrant Epithelial Reprogramming in Idiopathic Pulmonary Fibrosis using Human Induced Pluripotent Stem Cell-derived Alveolar Organoids

Project description:Alveolar type 2 (AT2) organoids, derived from induced pluripotent stem cells, were stimulated with a fibrosis cocktail containing the pro-fibrotic and inflammatory cytokines TGF-β (5 ng/ml), TNF-α (10 ng/ml), PDGF-AB (10 ng/ml) and LPA (5 μM) or control cocktail containing diluents for 72 h.

2023-05-22 | E-MTAB-11676 | biostudies-arrayexpress

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