Lineage-selective super enhancers mediate core regulatory circuitry during adipogenic and osteogenic differentiation of human mesenchymal stem cells
Abstract 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 h...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-10-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-05309-3 |
| _version_ | 1798030020075061248 |
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| author | Chen Wang Wen Tian Shou-Ye Hu Chen-Xi Di Chang-Yi He Qi-Long Cao Ruo-Han Hao Shan-Shan Dong Cong-Cong Liu Yu Rong Hua-Feng Kang Tie-Lin Yang Zhi Yang Yan Guo |
| author_facet | Chen Wang Wen Tian Shou-Ye Hu Chen-Xi Di Chang-Yi He Qi-Long Cao Ruo-Han Hao Shan-Shan Dong Cong-Cong Liu Yu Rong Hua-Feng Kang Tie-Lin Yang Zhi Yang Yan Guo |
| author_sort | Chen Wang |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-11T19:33:31Z |
| format | Article |
| id | doaj.art-ddbd2636d709473e958c08ccf374357c |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-11T19:33:31Z |
| publishDate | 2022-10-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-ddbd2636d709473e958c08ccf374357c2022-12-22T04:06:56ZengNature Publishing GroupCell Death and Disease2041-48892022-10-01131011210.1038/s41419-022-05309-3Lineage-selective super enhancers mediate core regulatory circuitry during adipogenic and osteogenic differentiation of human mesenchymal stem cellsChen Wang0Wen Tian1Shou-Ye Hu2Chen-Xi Di3Chang-Yi He4Qi-Long Cao5Ruo-Han Hao6Shan-Shan Dong7Cong-Cong Liu8Yu Rong9Hua-Feng Kang10Tie-Lin Yang11Zhi Yang12Yan Guo13Key Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi’an Jiaotong UniversityKey Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi’an Jiaotong UniversityHonghui Hospital, Xi’an Jiaotong UniversityKey Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi’an Jiaotong UniversityKey Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi’an Jiaotong UniversityKey Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi’an Jiaotong UniversityKey Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi’an Jiaotong UniversityKey Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi’an Jiaotong UniversityKey Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi’an Jiaotong UniversityKey Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi’an Jiaotong UniversityDepartment of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong UniversityKey Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi’an Jiaotong UniversityHonghui Hospital, Xi’an Jiaotong UniversityKey Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi’an Jiaotong UniversityAbstract 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.https://doi.org/10.1038/s41419-022-05309-3 |
| spellingShingle | Chen Wang Wen Tian Shou-Ye Hu Chen-Xi Di Chang-Yi He Qi-Long Cao Ruo-Han Hao Shan-Shan Dong Cong-Cong Liu Yu Rong Hua-Feng Kang Tie-Lin Yang Zhi Yang Yan Guo Lineage-selective super enhancers mediate core regulatory circuitry during adipogenic and osteogenic differentiation of human mesenchymal stem cells Cell Death and Disease |
| title | Lineage-selective super enhancers mediate core regulatory circuitry during adipogenic and osteogenic differentiation of human mesenchymal stem cells |
| title_full | Lineage-selective super enhancers mediate core regulatory circuitry during adipogenic and osteogenic differentiation of human mesenchymal stem cells |
| title_fullStr | Lineage-selective super enhancers mediate core regulatory circuitry during adipogenic and osteogenic differentiation of human mesenchymal stem cells |
| title_full_unstemmed | Lineage-selective super enhancers mediate core regulatory circuitry during adipogenic and osteogenic differentiation of human mesenchymal stem cells |
| title_short | Lineage-selective super enhancers mediate core regulatory circuitry during adipogenic and osteogenic differentiation of human mesenchymal stem cells |
| title_sort | lineage selective super enhancers mediate core regulatory circuitry during adipogenic and osteogenic differentiation of human mesenchymal stem cells |
| url | https://doi.org/10.1038/s41419-022-05309-3 |
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