Nanosecond pulsed electric fields enhance mesenchymal stem cells differentiation via DNMT1-regulated OCT4/NANOG gene expression
Abstract Background Multiple strategies have been proposed to promote the differentiation potential of mesenchymal stem cells (MSCs), which is the fundamental property in tissue formation and regeneration. However, these strategies are relatively inefficient that limit the application. In this study...
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| Format: | Article |
| Language: | English |
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BMC
2020-07-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-020-01821-5 |
| _version_ | 1818843215400271872 |
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| author | Kejia Li Tong Ning Hao Wang Yangzi Jiang Jue Zhang Zigang Ge |
| author_facet | Kejia Li Tong Ning Hao Wang Yangzi Jiang Jue Zhang Zigang Ge |
| author_sort | Kejia Li |
| collection | DOAJ |
| description | Abstract Background Multiple strategies have been proposed to promote the differentiation potential of mesenchymal stem cells (MSCs), which is the fundamental property in tissue formation and regeneration. However, these strategies are relatively inefficient that limit the application. In this study, we reported a novel and efficient strategy, nanosecond pulsed electric fields (nsPEFs) stimulation, which can enhance the trilineage differentiation potential of MSCs, and further explained the mechanism behind. Methods We used histological staining to screen out the nsPEFs parameters that promoted the trilineage differentiation potential of MSCs, and further proved the effect of nsPEFs by detecting the functional genes. In order to explore the corresponding mechanism, we examined the expression of pluripotency genes and the methylation status of their promoters. Finally, we targeted the DNA methyltransferase which was affected by nsPEFs. Results The trilineage differentiation of bone marrow-derived MSCs was significantly enhanced in vitro by simply pre-treating with 5 pulses of nsPEFs stimulation (energy levels as 10 ns, 20 kV/cm; 100 ns, 10 kV/cm), due to that the nsPEFs demethylated the promoters of stem cell pluripotency genes OCT4 and NANOG through instantaneous downregulation of DNA methylation transferase 1 (DNMT1), thereby increasing the expression of OCT4 and NANOG for up to 3 days, and created a treatment window period of stem cells. Conclusions In summary, nsPEFs can enhance MSCs differentiation via the epigenetic regulation and could be a safe and effective strategy for future stem cell application. |
| first_indexed | 2024-12-19T04:54:20Z |
| format | Article |
| id | doaj.art-ca520fa6d1db41b08bb3df87f40d1d13 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-19T04:54:20Z |
| publishDate | 2020-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-ca520fa6d1db41b08bb3df87f40d1d132022-12-21T20:35:17ZengBMCStem Cell Research & Therapy1757-65122020-07-0111111410.1186/s13287-020-01821-5Nanosecond pulsed electric fields enhance mesenchymal stem cells differentiation via DNMT1-regulated OCT4/NANOG gene expressionKejia Li0Tong Ning1Hao Wang2Yangzi Jiang3Jue Zhang4Zigang Ge5Department of Biomedical Engineering, College of Engineering, Peking UniversityDepartment of Biomedical Engineering, College of Engineering, Peking UniversityPeking-Tsinghua Center for Life Sciences, Peking UniversityInstitute for Tissue Engineering and Regenerative Medicine, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong KongInstitute of Biomechanics and Biomedical Engineering, College of Engineering, Peking UniversityDepartment of Biomedical Engineering, College of Engineering, Peking UniversityAbstract Background Multiple strategies have been proposed to promote the differentiation potential of mesenchymal stem cells (MSCs), which is the fundamental property in tissue formation and regeneration. However, these strategies are relatively inefficient that limit the application. In this study, we reported a novel and efficient strategy, nanosecond pulsed electric fields (nsPEFs) stimulation, which can enhance the trilineage differentiation potential of MSCs, and further explained the mechanism behind. Methods We used histological staining to screen out the nsPEFs parameters that promoted the trilineage differentiation potential of MSCs, and further proved the effect of nsPEFs by detecting the functional genes. In order to explore the corresponding mechanism, we examined the expression of pluripotency genes and the methylation status of their promoters. Finally, we targeted the DNA methyltransferase which was affected by nsPEFs. Results The trilineage differentiation of bone marrow-derived MSCs was significantly enhanced in vitro by simply pre-treating with 5 pulses of nsPEFs stimulation (energy levels as 10 ns, 20 kV/cm; 100 ns, 10 kV/cm), due to that the nsPEFs demethylated the promoters of stem cell pluripotency genes OCT4 and NANOG through instantaneous downregulation of DNA methylation transferase 1 (DNMT1), thereby increasing the expression of OCT4 and NANOG for up to 3 days, and created a treatment window period of stem cells. Conclusions In summary, nsPEFs can enhance MSCs differentiation via the epigenetic regulation and could be a safe and effective strategy for future stem cell application.http://link.springer.com/article/10.1186/s13287-020-01821-5Mesenchymal stem cellsNanosecond pulsed electric fieldsDemethylationDNMT1Biophysical stimulationStem cell differentiation |
| spellingShingle | Kejia Li Tong Ning Hao Wang Yangzi Jiang Jue Zhang Zigang Ge Nanosecond pulsed electric fields enhance mesenchymal stem cells differentiation via DNMT1-regulated OCT4/NANOG gene expression Stem Cell Research & Therapy Mesenchymal stem cells Nanosecond pulsed electric fields Demethylation DNMT1 Biophysical stimulation Stem cell differentiation |
| title | Nanosecond pulsed electric fields enhance mesenchymal stem cells differentiation via DNMT1-regulated OCT4/NANOG gene expression |
| title_full | Nanosecond pulsed electric fields enhance mesenchymal stem cells differentiation via DNMT1-regulated OCT4/NANOG gene expression |
| title_fullStr | Nanosecond pulsed electric fields enhance mesenchymal stem cells differentiation via DNMT1-regulated OCT4/NANOG gene expression |
| title_full_unstemmed | Nanosecond pulsed electric fields enhance mesenchymal stem cells differentiation via DNMT1-regulated OCT4/NANOG gene expression |
| title_short | Nanosecond pulsed electric fields enhance mesenchymal stem cells differentiation via DNMT1-regulated OCT4/NANOG gene expression |
| title_sort | nanosecond pulsed electric fields enhance mesenchymal stem cells differentiation via dnmt1 regulated oct4 nanog gene expression |
| topic | Mesenchymal stem cells Nanosecond pulsed electric fields Demethylation DNMT1 Biophysical stimulation Stem cell differentiation |
| url | http://link.springer.com/article/10.1186/s13287-020-01821-5 |
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