3D chromatin organization changes modulate adipogenesis and osteogenesis [ChIP-seq]

Human mesenchymal stem cells (hMSCs) can be differentiated into adipocytes and osteoblasts. While the transcriptomic and epigenomic changes during adipogenesis and osteogenesis have been characterized, what happens to the chromatin loops is hardly known. Here we induced hMSCs to adipogenic and osteogenic differentiation, and performed 2 kb resolution Hi-C experiments for loop detection and generated RNA-seq, histone modification ChIP-seq and ATAC-seq data for integrative analysis before and after differentiation. We quantitatively identified differential contact loops and unique loops. After integrating with multi-omics data, we demonstrate that strengthened loops after differentiation are associated with gene expression activation. Specially, unique loops are linked with cell fate determination. We also proposed loop-mediated regulatory networks and identified IRS2 and RUNX2 as being activated by cell-specific loops to facilitate adipocytes and osteoblasts commitment, respectively. These results are expected to help better understand the long-range regulation in controlling hMSC differentiation, and provide novel targets for studying adipocytes and osteoblasts determination. Hi-C experiment was conducted to reveal 3D chromatin changes before and after human mesenchymal stem cells differentiation into adipocytes and osteoblasts. Comprehensively profiling of gene expression, enhancer activity and chromatin accessibility using RNA-seq, H3K4me1 and H3K27ac ChIP-seq, and ATAC-seq were estimated at the same time.