Dynamic reorganization of nuclear architecture during human cardiogenesis [RNA-seq]

While chromosomal architecture varies among cell types, little is known about how this organization is established or its role in development. We integrated Hi-C, RNA-seq and ATAC-seq during cardiac differentiation from human pluripotent stem cells to generate a comprehensive profile of chromosomal architecture. We identified active and repressive domains that are dynamic during cardiogenesis and recapitulate in vivo cardiomyocytes. During differentiation, heterochromatic regions condense in cis. In contrast, many cardiac-specific genes, such as TTN (titin), transition to an active compartment coincident with upregulation. Moreover, we identify a network of genes, including TTN, that share the heart-specific splicing factor, RBM20, and become associated in trans during differentiation, suggesting the existence of a 3D nuclear splicing factory. Our results demonstrate both the dynamic nature in nuclear architecture and provide insights into how developmental genes are coordinately regulated. Overall design: Hi-C, RNA-seq and ATAC-seq analysis of four stages of human pluripotent stem cell differentiation to cardiomyocytes, including stem cell, mesoderm, cardiac progenitor, and cardiomyocyte, with two biological replicates of each condition. Hi-C and RNA-seq analysis of two biological replicates fetal heart samples.