Visualization and Analysis of Gene Expression in Calcific Aortic Valve Tissue Section by Spatial Transcriptomics

Abstract

Background: To identify the aortic valve spatial location information through spatial transcriptomics (ST) technology and explore the spatial expression and role in valve calcification of the key factors at the transcriptome-wide scales, thus providing new insight for clinical prevention and treatment of calcific aortic valve disease (CAVD). Methods: Six cases of human active valve stenosis calcified valves from valve replacement surgery and two cases of relatively normal aortic valves from heart transplantation were collected between March 1, 2021 and September 1, 2021. We constructed tissue-wide gene expression sequencing during aortic valve calcification formation using ST and performed comprehensive mapping of differentiation transitions and spatial expression information in the calcified area of the valve. Results: We identified 6736 genes based on the count level of gene expression at different locations and obtained the spatial distribution map of the three-layer structure of the main 9 cells of the aortic valve during the formation of valve calcification and proportions of aortic valves. Shear stress factors were significantly enriched in the aortic valve. The differential expression of TRP family genes was significantly based on spatial transcriptome analysis. Conclusion: Herein, we elucidated the spatial resolution of the transcriptome and tissue scope of the adult aortic valve, providing a basis for a better understanding of the cellular origin and complex cytopathological differentiation process of CAVD. Our findings further the understanding of the pathogenesis and heterogeneity of aortic valve calcification and the implementation of more effective personalized treatment methods.