4.6 Article

Cell landscape atlas for patients with chronic thromboembolic pulmonary hypertension after pulmonary endarterectomy constructed using single-cell RNA sequencing

Journal

AGING-US
Volume 13, Issue 12, Pages 16485-16499

Publisher

IMPACT JOURNALS LLC
DOI: 10.18632/aging.203168

Keywords

chronic thromboembolic pulmonary hypertension; single-cell RNA sequencing; gene ontology enrichment analysis

Funding

  1. National Natural Science Foundation of China [81300044, 31670928, 81871356, 81770253, 81370362, 81871328, 81900047]
  2. Beijing Natural Science Foundation [7162069, 7182149]
  3. Beijing Municipal Administration of Hospitals' Youth Programme [QML20160301]
  4. Open Foundation from Beijing Key Laboratory of Hypertension Research [2018GXY-KFKT-02]
  5. National Key Research and Development Program of China [2016YFC0905600]
  6. National Major Research Plan Training Program of China [91849111]
  7. Chinese Academy of Medical Sciences Central Public-interest Scientific Institution Basal Research Fund Young Medical Talents Award Project [2018RC320013]

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This study aimed to construct an atlas of the cell landscape and comprehensively characterize the cellular repertoire of pulmonary endarterectomized tissues in patients with CTEPH. Through single-cell RNA sequencing, the study identified 17 cell clusters classified into eight cell types, providing valuable insights into disease pathophysiology. Features of fibroblast/smooth muscle cells, endothelial cells, immune cells, and other cell types were significantly enriched with various functions, while CRISPLD2+ cell showed no significant enrichment, highlighting potential therapeutic targets.
This study aimed to construct an atlas of the cell landscape and comprehensively characterize the cellular repertoire of the pulmonary endarterectomized tissues of patients with chronic thromboembolic pulmonary hypertension (CTEPH). Five pulmonary endarterectomized tissues were collected. 10x Genomics single-cell RNA sequencing was performed, followed by the identification of cluster marker genes and cell types. Gene Ontology (GO) enrichment analysis was conducted. Seventeen cell clusters were characterized, corresponding to 10,518 marker genes, and then classified into eight cell types, including fibroblast/smooth muscle cell, endothelial cell, T cell/NK cell, macrophage, mast cell, cysteine rich secretory protein LCCL domain containing 2 (CRISPLD2)+ cell, cancer stem cell, and undefined. The specific marker genes of fibroblast/smooth muscle cell, endothelial cell, T cell/NK cell, macrophage, mast cell, and cancer stem cell were significantly enriched for multiple functions associated with muscle cell migration, endothelial cell migration, T cell activation, neutrophil activation, erythrocyte homeostasis, and tissue remodeling, respectively. No functions were significantly enriched for the marker gene of CRISPLD2+ cell. Our study, for the first time, provides an atlas of the cell landscape of the pulmonary endarterectomized tissues of CTEPH patients at single-cell resolution, which may serve as a valuable resource for further elucidation of disease pathophysiology.

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