We have developed and published a user-friendly computational 3D modeling tool that simulates positions of topologically-associated domains (TADs) relative to each other and to the nuclear periphery. The computational tool, called Chrom3D, integrates chromosome conformation capture (Hi-C) and lamin-associated domain (LAD) datasets to generate structure ensembles that recapitulate radial distributions of TADs detected in single cells. We use our tool to study the dynamic structural 4D reorganization of TADs during stem cell differentiation, using Hi-C and lamin ChIP-seq in multiple time steps. The resulting 4D models reveal TAD-TAD interactions involved in large scale dynamic alterations in chromatin architecture linked to gene expression changes across time points.