Single-cell transcriptomic analysis reveals differential cell subpopulations and distinct phenotype transition in normal and dissected ascending aorta

Molecular Medicine

Research Article

Jie Xing¹  Wen-rui Ma²  Guan-xin Zhang³  Xiao-bin Zhang⁴  Jian-feng Zhang⁴  Nai-shi Zhao⁴  Jing Zhang⁴  Yu-bin He⁴  Chong Wang⁴  Huang-dong Dai⁴  Yang-yang Zhang⁴  Jin-long Zhao⁵  Hai-zhen Jin⁶ 

[1] Department of Biobank, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China;Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, China;Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, No.168, Changhai Road, Shanghai, China;Department of Cardiovascular Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, No.241, West Huaihai Road, 200030, Shanghai, China;Department of Cardiovascular Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China;Department of Central Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China;

关键词: Single-cell RNA sequencing;    Acute thoracic aortic dissection;    Cell differentiation trajectory;    CXCL12;    Cell–cell interaction;    Phenotypic switch;   

DOI  :  10.1186/s10020-022-00584-4

 received in 2022-05-17, accepted in 2022-12-01,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundAcute thoracic aortic dissection (ATAD) is a fatal condition characterized by tear of intima, formation of false lumen and rupture of aorta. However, the subpopulations of normal and dissected aorta remain less studied.MethodsSingle-cell RNA sequencing was performed including 5 patients with ATAD and 4 healthy controls. Immunohistochemistry and immunofluorescence were used to verify the findings.ResultsWe got 8 cell types from human ascending aorta and identified 50 subpopulations including vascular smooth muscle cells (VSMCs), endothelial cells, fibroblasts, neutrophils, monocytes and macrophages. Six transmembrane epithelial antigen of prostate 4 metalloreductase (STEAP4) was identified as a new marker of synthetic VSMCs. CytoTRACE identified subpopulations with higher differentiation potential in specified cell types including synthetic VSMCs, enolase 1+ fibroblasts and myeloid-derived neutrophils. Synthetic VSMCs-derived C-X-C motif chemokine ligand 12 (CXCL12) might interact with neutrophils and fibroblasts via C-X-C motif chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3), respectively, which might recruit neutrophils and induce transdifferentitation of fibroblasts into synthetic VSMCs.ConclusionWe characterized signatures of different cell types in normal and dissected human ascending aorta and identified a new marker for isolation of synthetic VSMCs. Moreover, we proposed a potential mechanism that synthetic VSMCs might interact with neutrophils and fibroblasts via CXCL12-CXCR4/ACKR3 axis whereby deteriorating the progression of ATAD, which might provide new insights to better understand the development and progression of ATAD.

【 授权许可】

CC BY   
© The Author(s) 2022

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