Single-cell sequencing of mouse lung epithelial cells after bleomycin injury and modulation of IRE1α
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ABSTRACT:
PROVIDER: PRJNA1016394 | ENA |
REPOSITORIES: ENA
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Project description:Epithelial cells that are committed to a differentiated state in homeostasis can change their identity in response to injury. In the lung, alveolar type 2 (AT2) cells are the resident secretory epithelial cells of the alveolus, and after injury can proliferate and differentiate into type 1 cells. This inducible plasticity is central to alveolar regeneration, fibrosis, and malignancy, but the regulatory pathways that govern the balance between fate maintenance and differentiation are incompletely understood. Epithelial cells that are committed to a differentiated state in homeostasis can change their identity in response to injury. In the lung, alveolar type 2 (AT2) cells are the resident secretory epithelial cells of the alveolus, and after injury can proliferate and differentiate into type 1 cells. This inducible plasticity is central to alveolar regeneration, fibrosis, and malignancy, but the regulatory pathways that govern the balance between fate maintenance and differentiation are incompletely understood. IRE1α is an ER transmembrane protein conserved throughout eukaryotes that senses misfolded protein in the ER lumen and initiates cellular efforts to regain protein folding homeostasis through its cytosolic kinase and RNase domains. We previously showed that IRE1α pharmacologic or genetic loss of function decreased the accumulation of damage-associated transient progenitors (DATPs), and also promoted their differentiation into new alveolar epithelial cells. To further detail the functions of IRE1α after AT2 injury, we performed single-cell transcriptome profiling of the AT2-to-AT1 transition after bleomycin injury, with pharmacologic or epithelial-specific genetic loss of IRE1α function.
2025-08-12 | GSE243124 | GEO
Project description:Lung epithelial transcriptional responses to bleomycin and effects of IRE1α or TGFβ inhibition
| PRJNA788524 | ENA
Project description:This experiment sought to characterize the epithelial-specific transcriptional response in the bleomycin model of lung fibrosis, and the contribution of IRE1a and the TGFb-activating integrin avb6 to this response. "Ribotag" mice were crossed to ShhCre mice, both on the C57BL/6 background to generate experimental cohorts. Mice used for the experiment conditionally expressed HA-tagged ribosomal protein Rpl22 in the epithelium. Mice were exposed to intranasal bleomycin (3 U/kg) on day 1 and subsequently treated with the IRE1a kinase inhibitor KIRA8 (50 mg/kg daily), or the anti-integrin beta6 antibody 3G9 (10 mg/kg on day 1 and day 4). Treatment controls were either drug vehicle (3% ethanol, 7% Tween80, and 90% saline) or the inert antibody Axum8 in saline). Lungs were harvested on day 7 after bleomycin exposure, flash-frozen, and later homogenized under native conditions with cycloheximide. An aliquot of the “input” homogenate was removed and total RNA purified by Qiagen RNeasy Mini and is representative of the whole-lung transcriptome/translatome. The remaining homogenate was subjected to immunoprecipitation of HA-tagged polysomes, followed by RNA purification by Qiagen RNeasy Micro, and is representative of the lung epithelial transcriptome/translatome.
2022-02-14 | GSE190821 | GEO
Project description:Bleomycin-induced acute lung injury is characterized by mesenchymal cell activation, which leads to pulmonary fibrosis. They also have the potential to increase epithelial cells to regenerate alveolar epithelial cell integrity. We used microarrays to detail the change of global gene expression in lung mesenchymal cells in this process.
2022-09-15 | GSE208444 | GEO
Project description:Two single-cell RNA sequencing data sets were generated called "Whole lung" and "High Resolution". The "Whole lung" single-cell mRNAseq libraries were generated with Drop-Seq from whole mouse lungs upon bleomycin-induced injury and followed over time. Samples were taken at days 3 (n = 3), 7 (n = 5), 10 (n = 3), 14 (n = 4), 21 (n = 4) and 28 (n = 2). Control samples (n = 7) were administered saline only, also indicated with PBS or day0. The "High resolution" single-cell mRNAseq libraries were generated with Drop-Seq from the epithelial compartment of mouse lungs upon bleomycin-induced injury and followed over time. Samples were taken daily for two weeks and at days 21, 28, 36, 54 after injury. Control samples (n = 2) were administered saline only, also indicated with PBS or day0.
2019-12-02 | GSE141259 | GEO
Project description:We previously showed that pericyte-like cells derived from the FoxD1-lineage contribute to myofibroblasts following bleomycin-induced lung injury. However, their functional significance in lung fibrosis remains unknown. In this study, we used a model of lung pericyte-like cell ablation to test the hypothesis that pericyte-like cell ablation attenuates lung fibrosis in bleomycin-induced lung injury. Methods: Lung fibrosis was induced by intratracheal instillation of bleomycin. To ablate pericyte-like cells in the lung, diphtheria toxin (DT) was administered to Foxd1-Cre;Rosa26-iDTR mice at two different phases of bleomycin-induced lung injury. For early ablation, we co-administered bleomycin with DT and harvested mice at days 7 and 21. To test the effect of ablation after acute injury, we delivered DT 7 days after bleomycin administration. We assessed fibrosis by lung hydroxyproline content and semiquantitative analysis of picrosirius red-staining. We performed bronchoalveolar lavage to determine cell count and differential. We also interrogated genome-wide mRNA expression at day 7 post injury in whole lung RNA. We focused on the following cell populations for the transcriptional profiling experiments: FoxD1-derived+/Coll-GFP– pericytes (Peri), FoxD1-derived+/Coll-GFP+ pericytes (PeriFibro), and FoxD1-derived–/Coll-GFP+ stromal fibroblasts (Fibro).Results: Compared to DT-insensitive littermates where pericyte-like cells were not ablated, DT-sensitive animals exhibited no difference in fibrosis at day 21 both in the early and late pericyte ablation models. However, early ablation of pericytes reduced acute lung inflammation, as indicated by decreased inflammatory cells. Our data confirm a role for pericytes in regulating pulmonary inflammation in early lung injury.
2022-02-28 | GSE184761 | GEO
Project description:Drug-induced lung injury rarely, but seriously leads to severe lung diseases such as interstitial pneumonia and pulmonary fibrosis. However, the mechanism underlying drug-induced lung injury remains unclear. Anticancer drugs frequently induce pulmonary damage compared to the other categories of the drugs. In this study, the effect of bleomycin and methotrexate, which are representative pulmonary toxic anticancer drugs, on the comprehensive protein expression levels in alveolar epithelial model cell line, A549.
2025-07-25 | PXD053298 | Pride
Project description:Background and objective: The role of bronchiolar epithelial cells in the pathogenesis of pulmonary fibrosis has not been addressed. We previously demonstrated that DNA damage was found in bronchiole at early phase, and subsequently extended to alveolar cells at later phase in bleomycin-induced pulmonary fibrosis in mice. Club cells are progenitor cells for bronchiole, and are recognized to play protective roles against lung inflammation and damage. The aim of the study was to elucidate the role of club cells in the development of pulmonary fibrosis. Methods: C57BL/6J mice were received naphthalene intraperitoneally at day -2 to deplete club cells, and were given intratracheal bleomycin or vehicle at day 0. Lung tissues were obtained at day 1, 7, and 14, and bronchoalveolar lavage was performed at day 14. Gene expression was analysed from bronchiolar ephithelial cells sampled by laser captured microdissection at day 14. Results: Surprisingly, naphthalene-induced club cell depletion protected mice from bleomycin-induced lung injury and fibrosis. We conclude that club cells are involved in the development of lung injury and fibrosis.
2017-02-08 | GSE94522 | GEO
Project description:We applied next-generation sequencing to investigate the gene expression profiles in mouse alveolar epithelial cells (AECs). We identified a number of differentially regulated genes in the AECs of mice with bleomycin induced pulmonary fibrosis and LPS induced acute lung injury.
2018-02-01 | GSE109913 | GEO
Project description:Whole lung transcriptome from lung epithelial IRE1α knockout mice
| PRJNA788527 | ENA