1.4 COPD
COPD is the leading cause of respiratory death worldwide, and is also closely related to heart disease [27]. COPD is characterized by its persistent symptoms and destruction of lung parenchymal tissue, and especially during its advanced stages [28]. The cell-specific mechanisms underlying the pathobiology of COPD are not fully understood. ScRNA-seq has been used to obtain single-cell resolution and identify changes in COPD mechanisms, cell phenotypes, and alveolar niche crosstalk [29, 30]. Maor et al. [30] constructed single-cell RNA sequencing profiles of explants from subjects with advanced COPD or control lungs. Those profiles focused on three cell types associated with COPD pathogenesis: epithelial cells, endothelial cells, and alveolar macrophages. The profiles identified 33 abnormal types of basal cells, and identified the CXCL signal transduction that originates from endothelial cells via a network analysis, and found the common cell type specific transcriptional aberrations, and revealed that alveolar macrophages overexpressed metallothionein and HMOX1.
Recently, researchers analysis of 70,030 epithelial cells of lung adenocarcinoma (LUAD) and normal origin through single-cell RNA sequencing have identified the alveolar epithelial type II (AT2) cell subsets that express HHIP, and found that the capillary CXCL motif chemokine signal is an important cause of COPD alveolar inflammation. Another conclusion was that the alveolar macrophage subgroup of metallothionein is enriched in COPD, which provides a more profound understanding of COPD pathophysiology [31, 32]. At the same time, scRNA-seq was used to identify cell-specific differences and changes in individual protein levels that may contribute to the development of emphysema in severe COPD, More than 20,000 cells were assessed for cell type markers and cell-specific gene expression characteristics, from which IGFBP5 and QKI were identified as ciliated epithelial genes associated with severe COPD [33]. Based on the long-standing consensus that the immune response primarily mediates the pathology of chronic obstructive pulmonary disease (COPD), and that exosomes may be involved in the immune regulation of COPD, Research Scholars sequenced plasma exosomes and performed single-cell RNA sequencing on peripheral blood mononuclear cells (PBMCs) from patients with COPD and healthy controls,they identified 135 mRNAs, 132 lncRNAs, and 359 circRNAs from exosomes that were differentially expressed in six patients with COPD compared with four healthy controls, constructed competing endogenous RNA (ceRNA) and protein–protein interaction (PPI) networks to delineate the interactions between PBMCs and exosomes within COPD which has provided a more specific pathological process of COPD by enabling a series of data analyses of biological information, and constantly integrating cell types and their interactions.[34]