Comprehensive single-nucleus molecular and cell profiling features for cardiac tissues across platforms [10X_snRNAseq]

Single-nucleus RNA sequencing (snRNA-seq) enables transcriptomic profiling of complex tissues such as the heart, where dissociation into intact single cells is challenging. Among commercially available snRNA-seq platforms, 10x Genomics Chromium and Takara Bio’s ICELL8 cx represent technically distinct approaches, yet systematic comparisons in cardiac tissue are limited. Here, we benchmarked the 3′ Chromium, 5′ Chromium, and ICELL8 cx platforms using nuclei isolated from mouse and human heart tissues, including healthy donors and patients with non-ischemic cardiomyopathy. We assessed nuclei capture efficiency, library complexity, transcript detection sensitivity, RNA biotype coverage, ambient RNA contamination, and cell-type resolution. The Chromium platforms achieved higher nuclear throughput with robust capture efficiency and low ambient RNA contamination, whereas ICELL8 cx provided deeper transcriptomic coverage per nucleus, detecting a broader range of RNA biotypes, including low-abundance non-coding RNAs, albeit with lower nuclei yield. All platforms consistently resolved major cardiac cell populations. Together, these results inform selection of snRNA-seq workflows for cardiac tissue studies, highlighting trade-offs between cellular throughput and transcriptomic depth.