Journal
CELL DEATH AND DIFFERENTIATION
Volume -, Issue -, Pages -Publisher
SPRINGERNATURE
DOI: 10.1038/s41418-022-01035-7
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Funding
- Instrument Analysis Center of Xi'an Jiaotong University
- National Natural Science Foundation of China [82170896, 32170616, 31970569, 32100416, 31871264]
- Natural Science Basic Research Program of Shaanxi Province [2021JC-02]
- Innovation Capability Support Program of Shaanxi Province [2022TD-44]
- China Postdoctoral Science Foundation [2021M702618]
- Fundamental Research Funds for the Central Universities
- HighPerformance Computing Platform
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By comparing and analyzing adipogenesis and osteogenesis in human mesenchymal stem cells, we found that lineage-specific loops can activate gene expression and facilitate cell differentiation through the combination of enhancers and accessible chromatin. We also proposed loop-mediated regulatory networks and identified the controlling factors for adipocyte and osteoblast determination.
Human mesenchymal stem cells (hMSCs) can be differentiated into adipocytes and osteoblasts. The processes are driven by the rewiring of chromatin architectures and transcriptomic/epigenomic changes. Here, we induced hMSCs to adipogenic and osteogenic differentiation, and performed 2 kb resolution Hi-C experiments for chromatin loops detection. We also generated matched RNA-seq, ChIP-seq and ATAC-seq data for integrative analysis. After comprehensively comparing adipogenesis and osteogenesis, we quantitatively identified lineage-specific loops and screened out lineage-specific enhancers and open chromatin. We reveal that lineage-specific loops can activate gene expression and facilitate cell commitment through combining enhancers and accessible chromatin in a lineage-specific manner. We finally proposed loop-mediated regulatory networks and identified the controlling factors for adipocytes and osteoblasts determination. Functional experiments validated the lineage-specific regulation networks towards IRS2 and RUNX2 that are associated with adipogenesis and osteogenesis, respectively. These results are expected to help better understand the chromatin conformation determinants of hMSCs fate commitment.
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