Spatial Transcriptional Landscape of Human Heart Failure

Using the GeoMx whole human transcriptome digital spatial profiler, we spatially resolved gene expression profiles in failing human hearts, accounting for cell type and clinical and histological features. We first described how tissue segmentation using cell-type specific antibodies could reveal unique gene expression signatures of cardiomyocytes, endothelial cells, and fibroblasts in cardiac tissue. Second, gene regulation in HF appears to be cell-type specific and may even include signatures in opposing directions across cell types, which highlights the limitation of previous bulk transcriptional profiling. Third, spatial transcriptional profiling enabled us to find detailed gene expression signatures for typical histologic features related to HF. Lastly, additional consideration of histologic features in gene expression profiling on top of clinical information provides a unique resource for further research into the tipping point for irreversible structural changes in HF progression.