59 / 2026-04-02 15:51:08

Reorganization of 3D Genome Architecture Underlies Postnatal Mouse Cardiomyocyte Development

3D chromatin organization,postnatal heart development,cardiomyocyte maturation

During the postnatal development stage, mammalian cardiomyocytes undergo a critical transition characterized by changes in morphology, metabolism, and gene expression, alongside a rapid loss of proliferative capacity. This decline coincides with diminished regenerative potential, leaving the heart unable to repair injury. Although extensive transcriptional differences have been described, the mechanisms underlying this transition remain poorly understood, particularly at the level of higher-order chromatin organization. Here, we applied Hi-C to profile the 3D chromatin organization of cardiomyocytes at postnatal day 1 (P1), day 7 (P7), and day 56 (P56). We uncovered a global reorganization of chromatin architecture during postnatal development, with increased interchromosomal contacts and reduced long-range intrachromosomal interactions. These changes suggest a distance-dependent reorganization of chromatin interactions. At the compartment level, principal component 1 (PC1) values exhibited stage-specific alterations with P1 and P7 clustering distinctly from P56. These changes correlated with gene expression dynamics, indicating a quantitative reorganization of compartment structure during postnatal development. Furthermore, topologically associating domains (TADs) can be classified into sharp, intermediate, and extended structures, each displaying distinct alterations in insulation strength, consistent with remodeling of local chromatin domains during cell state transition.  Collectively, our findings reveal a multi-scale reorganization of 3D genome architecture during postnatal cardiac development. These results provide a structural framework for understanding how chromatin dynamics coordinate status transitions in the developing heart and how their dysregulation may contribute to cardiac disease.