Single-cell RNA sequencing reveals the contribution of smooth muscle cells and endothelial cells to fibrosis in human atrial tissue with atrial fibrillation.

Autor: An N; Guang'anmen Hospital, Chinese Academy of Chinese Medical Sciences, No.5 Beixian'ge Street, Xicheng District, Beijing, 100053, China.; Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, No.5 Haiyuncang, Dongcheng District, Beijing, 100700, China.; Beijing University of Chinese Medicine, Beijing, 100029, China., Yang F; Guang'anmen Hospital, Chinese Academy of Chinese Medical Sciences, No.5 Beixian'ge Street, Xicheng District, Beijing, 100053, China., Zhang G; Guang'anmen Hospital, Chinese Academy of Chinese Medical Sciences, No.5 Beixian'ge Street, Xicheng District, Beijing, 100053, China., Jiang Y; Guang'anmen Hospital, Chinese Academy of Chinese Medical Sciences, No.5 Beixian'ge Street, Xicheng District, Beijing, 100053, China., Liu H; Beijing University of Chinese Medicine, Beijing, 100029, China., Gao Y; Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, No.5 Haiyuncang, Dongcheng District, Beijing, 100700, China., Li Y; Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China., Ji P; Computational Genomics Lab, Beijing Institutes of Life Science, Chinese Academy of Sciences, No. 5, Yard 1, Beichen West Road, Chaoyang District, Beijing, 100101, China. jipeifeng@biols.ac.cn., Shang H; Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, No.5 Haiyuncang, Dongcheng District, Beijing, 100700, China. shanghongcai@126.com., Xing Y; Guang'anmen Hospital, Chinese Academy of Chinese Medical Sciences, No.5 Beixian'ge Street, Xicheng District, Beijing, 100053, China. xingyanwei12345@163.com.
Jazyk: angličtina
Zdroj: Molecular medicine (Cambridge, Mass.) [Mol Med] 2024 Dec 19; Vol. 30 (1), pp. 247. Date of Electronic Publication: 2024 Dec 19.
DOI: 10.1186/s10020-024-00999-1
Abstrakt: Aims: Atrial fibrillation (AF) has high mortality and morbidity rates. However, the intracellular molecular complexity of the atrial tissue of patients with AF has not been adequately assessed.
Methods and Results: We investigated the cellular heterogeneity of human atrial tissue and changes in differentially expressed genes between cells using single-cell RNA sequencing, fluorescence in situ hybridization, intercellular communication, and cell trajectory analysis. Using genome-wide association studies (GWAS) and proteomics, we discovered cell types enriched for AF susceptibility genes. We discovered eight different cell types, which were further subdivided into 23 subpopulations. In AF, the communication strength between smooth muscle cells (SMCs) and fibroblast (FB) 3 cells increased and the relevant signaling pathways were quite similar. Subpopulations of endothelial cells (ECs) are mainly involved in fibrosis through TXNDC5 and POSTN. AF susceptibility genes revealed by GWAS were especially enriched in neuronal and epicardial cells, FB3, and lymphoid (Lys) cells, whereas proteomic sequencing differential proteins were concentrated in FB3 cells and SMCs.
Conclusions: This study provides a cellular landscape based on the atrial tissue of patients with AF and highlights intercellular changes and differentially expressed genes that occur during the disease process. A thorough description of the cellular populations involved in AF will facilitate the identification of new cell-based interventional targets with direct functional significance for the treatment of human disease.
Competing Interests: Declarations. Ethics approval and consent to participate: All experimental protocols were approved by the Ethics Committee of Guang’anmen Hospital, Chinese Academy of Chinese Medical Sciences (no. 2021-106-KY). Furthermore, the study was conducted in accordance with the principles of the Declaration of Helsinki. Each patient or their families signed an informed consent before enrollment that clearly stated the purpose of our study. Patient demographics and characteristics are listed in Table S1. Consent for publication: All authors are consentient for publication. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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