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.

中文翻译：

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3D染色质组织变化调节脂肪形成和成骨

人间充质干细胞（hMSCs）可以分化为脂肪细胞和成骨细胞。虽然已经表征了脂肪形成和成骨过程中的转录组和表观基因组变化，但染色质环发生了什么却鲜为人知。在这里，我们诱导hMSCs进行成脂和成骨分化，并进行了2 kb分辨率的Hi-C实验用于环检测，并生成了RNA-seq，组蛋白修饰ChIP-seq和ATAC-seq数据，用于分化前后的整合分析。我们定量地确定了差分接触回路和独特回路。与多组学数据整合后，我们证明分化后增强的环与基因表达激活相关。特别地，独特的循环与细胞命运的确定联系在一起。我们还提出了环介导的调控网络，并确定IRS2和RUNX2被细胞特异性环激活，以分别促进脂肪细胞和成骨细胞的定向。这些结果有望帮助更好地了解控制hMSC分化的远程调控，并为研究脂肪细胞和成骨细胞提供新的靶标。