Histone demethylase JMJD6 regulates cellular migration and proliferation in adipose-derived mesenchymal stem cells
Abstract Background Adipose-derived mesenchymal stem cells (ADSCs) have been extensively explored as a promising therapeutic agent due to their differentiation, proliferation and migration abilities. The epigenetic mechanisms that regulate the fate of mesenchymal stem cells (MSCs) have been describe...
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| Format: | Article |
| Language: | English |
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BMC
2018-08-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-018-0949-3 |
| _version_ | 1819068842324787200 |
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| author | Chongyang Shen Qingli Quan Chuan Yang Yueqiang Wen Hong Li |
| author_facet | Chongyang Shen Qingli Quan Chuan Yang Yueqiang Wen Hong Li |
| author_sort | Chongyang Shen |
| collection | DOAJ |
| description | Abstract Background Adipose-derived mesenchymal stem cells (ADSCs) have been extensively explored as a promising therapeutic agent due to their differentiation, proliferation and migration abilities. The epigenetic mechanisms that regulate the fate of mesenchymal stem cells (MSCs) have been described in detail. However, the epigenetic modulation of ADSCs proliferation and migration is poorly understood. Methods The present study examined histone demethylases roles and expression by RT-PCR, as well as through siRNA screening and ChIP-qPCR assay. Cellular proliferation and migration assays were employed in shRNA-mediated JMJD6 knockdown and control ADSCs. PDE1C inhibition studies were conducted to confirm its role in JMJD6-mediated epigenetic regulation of ADSCs. Results The data demonstrate that the histone demethylase JMJD6 plays a critical role in regulating the proliferation and migration of ADSCs by removing H4R3me2a at the promoter regions of PDEC1 and suppressing PDEC1 expression. Importantly, the depletion of JMJD6 in ADSCs significantly increased cellular proliferation and motility, which was associated with increases in PDE1C expression and decreases in the levels of both cAMP and cGMP. The increase in proliferation and migration was reversed by treatment with a PDE1C inhibitor, suggesting that JMJD6 attenuates the proliferation and migration of ADSCs as an epigenetic regulator and PDE1C partially contributes to the JMJD6-mediated regulation. Conclusions Taken together, our results indicate for the first time that JMJD6 plays an important role in the regulation of ADSCs proliferation and migration through the modulation of PDE1C expression. |
| first_indexed | 2024-12-21T16:40:34Z |
| format | Article |
| id | doaj.art-db48d876c3934890b3399bf67f2f2381 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-21T16:40:34Z |
| publishDate | 2018-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-db48d876c3934890b3399bf67f2f23812022-12-21T18:57:07ZengBMCStem Cell Research & Therapy1757-65122018-08-019111310.1186/s13287-018-0949-3Histone demethylase JMJD6 regulates cellular migration and proliferation in adipose-derived mesenchymal stem cellsChongyang Shen0Qingli Quan1Chuan Yang2Yueqiang Wen3Hong Li4Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education, West China Second University Hospital, Sichuan UniversityWest China Hospital, Sichuan UniversityKey Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education, West China Second University Hospital, Sichuan UniversityBasic Medicine School, Chengdu University of Traditional Chinese MedicineKey Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education, West China Second University Hospital, Sichuan UniversityAbstract Background Adipose-derived mesenchymal stem cells (ADSCs) have been extensively explored as a promising therapeutic agent due to their differentiation, proliferation and migration abilities. The epigenetic mechanisms that regulate the fate of mesenchymal stem cells (MSCs) have been described in detail. However, the epigenetic modulation of ADSCs proliferation and migration is poorly understood. Methods The present study examined histone demethylases roles and expression by RT-PCR, as well as through siRNA screening and ChIP-qPCR assay. Cellular proliferation and migration assays were employed in shRNA-mediated JMJD6 knockdown and control ADSCs. PDE1C inhibition studies were conducted to confirm its role in JMJD6-mediated epigenetic regulation of ADSCs. Results The data demonstrate that the histone demethylase JMJD6 plays a critical role in regulating the proliferation and migration of ADSCs by removing H4R3me2a at the promoter regions of PDEC1 and suppressing PDEC1 expression. Importantly, the depletion of JMJD6 in ADSCs significantly increased cellular proliferation and motility, which was associated with increases in PDE1C expression and decreases in the levels of both cAMP and cGMP. The increase in proliferation and migration was reversed by treatment with a PDE1C inhibitor, suggesting that JMJD6 attenuates the proliferation and migration of ADSCs as an epigenetic regulator and PDE1C partially contributes to the JMJD6-mediated regulation. Conclusions Taken together, our results indicate for the first time that JMJD6 plays an important role in the regulation of ADSCs proliferation and migration through the modulation of PDE1C expression.http://link.springer.com/article/10.1186/s13287-018-0949-3Histone demethylaseJMJD6ADSCsMigrationProliferation |
| spellingShingle | Chongyang Shen Qingli Quan Chuan Yang Yueqiang Wen Hong Li Histone demethylase JMJD6 regulates cellular migration and proliferation in adipose-derived mesenchymal stem cells Stem Cell Research & Therapy Histone demethylase JMJD6 ADSCs Migration Proliferation |
| title | Histone demethylase JMJD6 regulates cellular migration and proliferation in adipose-derived mesenchymal stem cells |
| title_full | Histone demethylase JMJD6 regulates cellular migration and proliferation in adipose-derived mesenchymal stem cells |
| title_fullStr | Histone demethylase JMJD6 regulates cellular migration and proliferation in adipose-derived mesenchymal stem cells |
| title_full_unstemmed | Histone demethylase JMJD6 regulates cellular migration and proliferation in adipose-derived mesenchymal stem cells |
| title_short | Histone demethylase JMJD6 regulates cellular migration and proliferation in adipose-derived mesenchymal stem cells |
| title_sort | histone demethylase jmjd6 regulates cellular migration and proliferation in adipose derived mesenchymal stem cells |
| topic | Histone demethylase JMJD6 ADSCs Migration Proliferation |
| url | http://link.springer.com/article/10.1186/s13287-018-0949-3 |
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