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Single-cell sequencing highlights increased atypical AT2 interacting with M1 macrophage in COPD

ABSTRACT: Single-cell sequencing highlights increased atypical AT2 interacting with M1 macrophage in COPD

PROVIDER: PRJNA1127657 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29528317.fastq.gz	Fastqsanger.gz
	SRR29528318.fastq.gz	Fastqsanger.gz
	SRR29528319_1.fastq.gz	Fastqsanger.gz
	SRR29528319_2.fastq.gz	Fastqsanger.gz
	SRR29528320_1.fastq.gz	Fastqsanger.gz

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Single-cell sequencing highlights increased atypical AT2 interacting with M1 macrophage in COPD

Project description:We have constructed a transcriptomic map of airways using lung tissues from three COPD (GOLD grade I) who underwent surgical resection for lung cancer. We performed 5' single-cell RNA sequencing (scRNA-seq) on three COPD and three control matched lung tissue, as well as the organoid samples.

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Extracellular Vesicle Cargo from Lipofibroblasts Mitigates COPD by Alveolar Type II Cell Restoration

Project description:Rationale: Emerging research highlights cellular abnormalities in Chronic Obstructive Pulmonary Disease (COPD), focusing on alveolar type 2 (AT2) cells, which are key to lung tissue repair and normal cellular differentiation. Lipofibroblasts (LipoFBs), stromal fibroblasts containing lipid droplets, are closely associated with AT2 cells and support their function. Objectives: We present a comprehensive investigation into the therapeutic potential of extracellular vesicles (EVs) derived from LipoFBs (LipoFB-EVs) in COPD treatment. Methods: LipoFBs were induced from lung fibroblasts using Metformin or Rosiglitazone in vitro, and their EVs were isolated via ultracentrifugation for analysis. Main Results: They effectively mitigate key COPD pathologies such as cellular senescence and inflammatory responses in lung epithelial cells. This is achieved by reducing reactive oxygen species (ROS) levels and modulating DNA damage response pathways. Moreover, LipoFB-EVs demonstrate anti-fibrotic properties by inhibiting TGF-β-induced myofibroblast differentiation, surpassing conventional anti-fibrotic drugs. They also aid in restoring impaired AT2 stem cells, which are crucial for lung homeostasis, by enhancing their viability, colony-forming ability, and proliferation. Furthermore, we identify the presence of L-type amino acid transporter 1 (LAT1) within LipoFB-EVs, which mediates amino acid uptake, particularly leucine transport, and contributes to the restoration of AT2 cell dysfunction. Importantly, the administration of LipoFB-EVs in murine models of COPD resulted in significant improvements in airway inflammation, remodeling, obstruction, cellular senescence, and alveolar emphysema induced by both short- and long-term CS exposure. Conclusions: Our findings highlight the therapeutic potential of LipoFB-EVs as a novel regenerative therapy for COPD, offering promising avenues for future clinical interventions

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RNA-sequencing across three matched tissues highlights gene expression signatures in COPD

Project description:RNA-sequencing across three matched tissues highlights gene expression signatures in COPD

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RNA-sequencing across three matched tissues highlights gene expression signatures in COPD

Project description:Multiple gene expression studies have been performed separately in peripheral blood, lung, and airway tissues to study COPD. We performed RNA-sequencing gene expression profiling of large-airway epithelium, alveolar macrophage and peripheral blood samples from the same set of COPD cases and controls from the COPDGene study who underwent bronchoscopy at a single center. Using statistical and gene set enrichment approaches, we sought to improve the understanding of COPD by studying gene sets and pathways across these tissues, beyond the individual genomic determinants.

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Project description:Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and structural remodelling across different anatomical structures of the lung, including airways, parenchyma, and pulmonary vessels. However, compartment specific changes in immune cells composition and their communications with underlying structural cells is under investigated. Our study sought to assess the spatially resolved cellular organization of healthy and advanced end-stage COPD lungs using Visium spatial transcriptomics. We generated spatial transcriptomic map that uncovered distinct COPD-associated niches, characterized by increased neutrophils and myofibroblast with pronounced extracellular matrix organization around vessels, and colocalization of cytotoxic T cells and their interaction with alveolar type 2 cells and goblet cells, driving stress-induced cytotoxic response in the parenchyma and epithelial differentiation in the airway, respectively. Overall, our findings provide novel insights into compartment-specific cellular microenvironments that contribute to tissue remodelling processes in COPD.

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Spatial Transcriptomics Reveals Compartment-Specific Cytotoxic T cells Crosstalk with AT2 and Goblet cells in Advanced COPD

Project description:Spatial Transcriptomics Reveals Compartment-Specific Cytotoxic T cells Crosstalk with AT2 and Goblet cells in Advanced COPD

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