Transciptional profile of pericytes and stromal cells in bleomycin lung injury
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ABSTRACT:
PROVIDER: PRJNA766070 | ENA |
REPOSITORIES: ENA
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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:Analysis of epigenetic changes of pericytes after ischemia-reperfusion renal injury. The hypothesis tested in the present study was that epigenetic change develope in pericytes after acute kidney injury. This phenotype change would cause pericyte to be more proliferative and profibrotic. Results provide important information of the epigenetic change of pericytes, such as specific mechano-responsive genes, up-regulated specific proliferative and profibrotic functions.
2019-12-05 | GSE140988 | GEO
Project description:The meningeal transciptional response to traumatic brain injury and aging
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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:Epigenetic changes of pericytes after ischemia-reperfusion renal injury
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Project description:Fibrotic scar tissue formation is conserved throughout the central nervous system in humans and mice, and impairs tissue regeneration and functional recovery. However, the origin of scar-forming stromal fibroblasts is controversial. Here, we show that stromal fibroblasts found after spinal cord injury derive from two populations of perivascular cells that are anatomically and transcriptionally defined as pericytes and perivascular fibroblasts. We identify two distinct perivascular cell populations, which activate and transcriptionally converge on the generation of stromal myofibroblasts after injury. Our results suggest potential targets to improve tissue regeneration and functional recovery after central nervous system injuries.
2024-05-10 | GSE229916 | 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:Fibrotic scar tissue formation is conserved throughout the central nervous system in humans and mice, and impairs tissue regeneration and functional recovery. However, the origin of scar-forming stromal fibroblasts is controversial. Here, we show that stromal fibroblasts found after spinal cord injury derive from two populations of perivascular cells that are anatomically and transcriptionally defined as pericytes and perivascular fibroblasts. We identify two distinct perivascular cell populations, which activate and transcriptionally converge on the generation of stromal myofibroblasts after injury. Our results suggest potential targets to improve tissue regeneration and functional recovery after central nervous system injuries.
2024-05-10 | GSE266250 | GEO
Project description:Fibrotic scar tissue formation is conserved throughout the central nervous system in humans and mice, and impairs tissue regeneration and functional recovery. However, the origin of scar-forming stromal fibroblasts is controversial. Here, we show that stromal fibroblasts found after spinal cord injury derive from two populations of perivascular cells that are anatomically and transcriptionally defined as pericytes and perivascular fibroblasts. We identify two distinct perivascular cell populations, which activate and transcriptionally converge on the generation of stromal myofibroblasts after injury. Our results suggest potential targets to improve tissue regeneration and functional recovery after central nervous system injuries.
2024-05-10 | GSE266251 | GEO
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