Spatial Transcriptomics in Human Cardiac Tissue

Abstract

Spatial transcriptomics has transformed our understanding of gene expression by preserving the spatial context within tissues. This review focuses on the application of spatial transcriptomics in human cardiac tissues, exploring current technologies with a focus on commercially available platforms. We also highlight key studies utilizing spatial transcriptomics to investigate cardiac development, electro-anatomy, immunology, and ischemic heart disease. These studies demonstrate how spatial transcriptomics can be used in conjunction with other omics technologies to provide a more comprehensive picture of human health and disease. Despite its transformative potential, spatial transcriptomics comes with several challenges that limit its widespread adoption and broader application. By addressing these limitations and fostering interdisciplinary collaboration, spatial transcriptomics has the potential to become an essential tool in cardiovascular research. We hope this review serves as a practical guide for researchers interested in adopting spatial transcriptomics, particularly those with limited prior experience, by providing insights into current technologies, applications, and considerations for successful implementation.

Keywords: CosMX; CurioSeeker; GeoMX; MERSCOPE; Molecular Cartography; STomics; Visium; Xenium; cardiovascular diseases; spatial transcriptomics.

Figure 1

Workflow of spatial transcriptomics, outlining tissue preparation, slide preparation, data acquisition, data analysis, and downstream biological applications. The process begins with tissue preparation from fresh frozen, fixed frozen, or formalin-fixed paraffin-embedded (FFPE) samples. Sequencing-based methods use spatial barcodes to preserve spatial locations of transcripts and next-generation sequencing (NGS) to identify transcripts. In situ sequencing (ISS) relies on rolling circle amplification (RCA) to anchor and amplify complementary DNA (cDNA) while retaining the spatial context. Fluorescently labeled oligonucleotide probes then hybridize to cDNA using sequencing by ligation. In situ hybridization (ISH) methods detect target sequences by hybridization of complementary fluorescent probes. The product of spatial transcriptomics is the gene expression matrix with spatial reconstruction to address key biological questions such as cell composition, cell-cell interactions, and molecular interactions. FFPE, formalin-fixed paraffin-embedded; ISH, in situ hybridization; ISS, in situ sequencing; NGS, next-generation sequencing; RCA, rolling circle amplification.