Lineage-selective super enhancers mediate core regulatory circuitry during adipogenic and osteogenic differentiation of human mesenchymal stem cells.
Lineage-selective super enhancers mediate core regulatory circuitry during adipogenic and osteogenic differentiation of human mesenchymal stem cells.
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DOI：
10.1038/s41419-022-05309-3
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发表时间：
2022-10-12
影响因子：
9
通讯作者：
Guo, Yan
中科院分区：
文献类型：
--
作者：
Wang, Chen;Tian, Wen;Hu, Shou-Ye;Di, Chen-Xi;He, Chang-Yi;Cao, Qi-Long;Hao, Ruo-Han;Dong, Shan-Shan;Liu, Cong-Cong;Rong, Yu;Kang, Hua-Feng;Yang, Tie-Lin;Yang, Zhi;Guo, Yan
Human mesenchymal stem cells (hMSCs) can be differentiated into osteoblasts and adipocytes. During these processes, super enhancers (SEs) play important roles. Here, we performed comprehensive characterization of the SEs changes associated with adipogenic and osteogenic differentiation of hMSCs, and revealed that SEs changed more dramatically compared with typical enhancers. We identified a set of lineage-selective SEs, whose target genes were enriched with cell type-specific functions. Functional experiments in lineage-selective SEs demonstrated their specific roles in directed differentiation of hMSCs. We also found that some key transcription factors regulated by lineage-selective SEs could form core regulatory circuitry (CRC) to regulate each other’s expression and control the hMSCs fate determination. In addition, we found that GWAS SNPs of osteoporosis and obesity were significantly enriched in osteoblasts-selective SEs or adipocytes-selective SEs, respectively. Taken together, our studies unveiled important roles of lineage-selective SEs in hMSCs differentiation into osteoblasts and adipocytes.
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影响因子：
30.8
作者：
Lee D;Gorkin DU;Baker M;Strober BJ;Asoni AL;McCallion AS;Beer MA
通讯作者：
Beer MA
影响因子：
12.4
作者：
Chen Q;Shou P;Zheng C;Jiang M;Cao G;Yang Q;Cao J;Xie N;Velletri T;Zhang X;Xu C;Zhang L;Yang H;Hou J;Wang Y;Shi Y
通讯作者：
Shi Y
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
影响因子：
30.8
作者：
Fulco, Charles P.;Nasser, Joseph;Engreitz, Jesse M.
通讯作者：
Engreitz, Jesse M.