Single-cell and Spatial Heterogeneity Landscapes of Mature Epicardial Cells

Overview

Journal J Pharm Anal

Specialty Chemistry

Date 2023 Sep 18

PMID 37719196

Authors

Jianlin Du

Xin Yuan

Haijun Deng

Rongzhong Huang

Bin Liu

Tianhua Xiong

Xianglin Long

Ling Zhang

Yingrui Li

Qiang She

Affiliations

Soon will be listed here.

Abstract

, , and have been identified as epicardial markers during the early embryonic stage. However, the gene markers of mature epicardial cells remain unclear. Single-cell transcriptomic analysis was performed with the Seurat, Monocle, and CellphoneDB packages in R software with standard procedures. Spatial transcriptomics was performed on chilled Visium Tissue Optimization Slides (10x Genomics) and Visium Spatial Gene Expression Slides (10x Genomics). Spatial transcriptomics analysis was performed with Space Ranger software and R software. Immunofluorescence, whole-mount RNA in situ hybridization and X-gal staining were performed to validate the analysis results. Spatial transcriptomics analysis revealed distinct transcriptional profiles and functions between epicardial tissue and non-epicardial tissue. Several gene markers specific to postnatal epicardial tissue were identified, including , , , and . Single-cell transcriptomic analysis revealed that cardiac cells from wildtype mouse hearts (from embryonic day 9.5 to postnatal day 9) could be categorized into six major cell types, which included epicardial cells. Throughout epicardial development, , , and were consistently expressed, whereas genes including , , and exhibited increased expression during the mature stages of development. Pseudotime analysis further revealed two epicardial cell fates during maturation. Moreover, , , , and positive epicardial cells were enriched in extracellular matrix signaling. Our results suggested , , , , and other genes were mature epicardium markers. Extracellular matrix signaling was found to play a critical role in the mature epicardium, thus suggesting potential therapeutic targets for heart regeneration in future clinical practice.

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