Mapping Chamber Bias and Microanatomical Niches in Human Ventricular Development
Nayeon Kim *
Biomedical Sciences Division, STEM Science Center, 111 Charlotte Place, Englewood Cliffs, NJ 07632, United States of America.
*Author to whom correspondence should be addressed.
Abstract
A chamber-, time-, and niche-aware spatial transcriptomic analysis of human ventricular development spanning 13 to15 post-conception weeks (PCW) was performed. Using the Farah et al. atlas as a scaffold, we reproduced major cardiac lineages and applied pseudobulk differential expression with false discovery rate (FDR) control, cross-checked against single-cell contrasts, to quantify left–right asymmetry and temporal change. At 13 PCW, left ventricle (LV)-biased programs contrasted with right ventricle (RV)-biased signatures, indicating broad chamber-specific regulation rather than isolated outliers. Across 13 to 15 PCW, maturation was dominated by global consolidation with selective increases and decreases. Spatial neighborhood metrics—including cell–cell enrichment, nearest-neighbor distances, and cardiomyocyte-centric partner profiles—mapped coherent niches linking trabecular cardiomyocytes with endocardium and compact cardiomyocytes with fibroblast/pericyte compartments, and separated conduction and non-canonical cardiomyocyte (CM) classes into distinct microenvironments. Together, these results connect chamber-biased and temporal gene programs to reproducible tissue neighborhoods during ventricular maturation, yielding a quantitative framework and machine-readable outputs for mechanistic studies of human cardiac development.
Keywords: Cardiac microenvironment, chamber-specific regulation, gene expression dynamics, spatial transcriptomics, ventricular development