Nitro-Oleic Acid Inhibits Stemness Maintenance and Enhances Neural Differentiation of Mouse Embryonic Stem Cells via STAT3 Signaling
Nitro-oleic acid (NO<sub>2</sub>-OA), pluripotent cell-signaling mediator, was recently described as a modulator of the signal transducer and activator of transcription 3 (STAT3) activity. In our study, we discovered new aspects of NO<sub>2</sub>-OA involvement in the regulat...
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MDPI AG
2021-09-01
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| Online Access: | https://www.mdpi.com/1422-0067/22/18/9981 |
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| author | Jana Pereckova Michaela Pekarova Nikoletta Szamecova Zuzana Hoferova Kristyna Kamarytova Martin Falk Tomas Perecko |
| author_facet | Jana Pereckova Michaela Pekarova Nikoletta Szamecova Zuzana Hoferova Kristyna Kamarytova Martin Falk Tomas Perecko |
| author_sort | Jana Pereckova |
| collection | DOAJ |
| description | Nitro-oleic acid (NO<sub>2</sub>-OA), pluripotent cell-signaling mediator, was recently described as a modulator of the signal transducer and activator of transcription 3 (STAT3) activity. In our study, we discovered new aspects of NO<sub>2</sub>-OA involvement in the regulation of stem cell pluripotency and differentiation. Murine embryonic stem cells (mESC) or mESC-derived embryoid bodies (EBs) were exposed to NO<sub>2</sub>-OA or oleic acid (OA) for selected time periods. Our results showed that NO<sub>2</sub>-OA but not OA caused the loss of pluripotency of mESC cultivated in leukemia inhibitory factor (LIF) rich medium via the decrease of pluripotency markers (NANOG, sex-determining region Y-box 1 transcription factor (SOX2), and octamer-binding transcription factor 4 (OCT4)). The effects of NO<sub>2</sub>-OA on mESC correlated with reduced phosphorylation of STAT3. Subsequent differentiation led to an increase of the ectodermal marker orthodenticle homolog 2 (<i>Otx2</i>). Similarly, treatment of mESC-derived EBs by NO<sub>2</sub>-OA resulted in the up-regulation of both neural markers <i>Nestin</i> and β-Tubulin class III (<i>Tubb3</i>). Interestingly, the expression of cardiac-specific genes and beating of EBs were significantly decreased. In conclusion, NO<sub>2</sub>-OA is able to modulate pluripotency of mESC via the regulation of STAT3 phosphorylation. Further, it attenuates cardiac differentiation on the one hand, and on the other hand, it directs mESC into neural fate. |
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| spelling | doaj.art-b68695ed57fb42ee96c4c4ff608ed3d02023-11-22T13:30:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-012218998110.3390/ijms22189981Nitro-Oleic Acid Inhibits Stemness Maintenance and Enhances Neural Differentiation of Mouse Embryonic Stem Cells via STAT3 SignalingJana Pereckova0Michaela Pekarova1Nikoletta Szamecova2Zuzana Hoferova3Kristyna Kamarytova4Martin Falk5Tomas Perecko6Institute of Biophysics of the Czech Academy of Sciences, Department of Cell Biology and Radiobiology, Kralovopolska 135, 612 65 Brno, Czech RepublicInstitute of Biophysics of the Czech Academy of Sciences, Department of Cell Biology and Radiobiology, Kralovopolska 135, 612 65 Brno, Czech RepublicInstitute of Biophysics of the Czech Academy of Sciences, Department of Cell Biology and Radiobiology, Kralovopolska 135, 612 65 Brno, Czech RepublicInstitute of Biophysics of the Czech Academy of Sciences, Department of Cell Biology and Radiobiology, Kralovopolska 135, 612 65 Brno, Czech RepublicInstitute of Biophysics of the Czech Academy of Sciences, Department of Cell Biology and Radiobiology, Kralovopolska 135, 612 65 Brno, Czech RepublicInstitute of Biophysics of the Czech Academy of Sciences, Department of Cell Biology and Radiobiology, Kralovopolska 135, 612 65 Brno, Czech RepublicInstitute of Biophysics of the Czech Academy of Sciences, Department of Cell Biology and Radiobiology, Kralovopolska 135, 612 65 Brno, Czech RepublicNitro-oleic acid (NO<sub>2</sub>-OA), pluripotent cell-signaling mediator, was recently described as a modulator of the signal transducer and activator of transcription 3 (STAT3) activity. In our study, we discovered new aspects of NO<sub>2</sub>-OA involvement in the regulation of stem cell pluripotency and differentiation. Murine embryonic stem cells (mESC) or mESC-derived embryoid bodies (EBs) were exposed to NO<sub>2</sub>-OA or oleic acid (OA) for selected time periods. Our results showed that NO<sub>2</sub>-OA but not OA caused the loss of pluripotency of mESC cultivated in leukemia inhibitory factor (LIF) rich medium via the decrease of pluripotency markers (NANOG, sex-determining region Y-box 1 transcription factor (SOX2), and octamer-binding transcription factor 4 (OCT4)). The effects of NO<sub>2</sub>-OA on mESC correlated with reduced phosphorylation of STAT3. Subsequent differentiation led to an increase of the ectodermal marker orthodenticle homolog 2 (<i>Otx2</i>). Similarly, treatment of mESC-derived EBs by NO<sub>2</sub>-OA resulted in the up-regulation of both neural markers <i>Nestin</i> and β-Tubulin class III (<i>Tubb3</i>). Interestingly, the expression of cardiac-specific genes and beating of EBs were significantly decreased. In conclusion, NO<sub>2</sub>-OA is able to modulate pluripotency of mESC via the regulation of STAT3 phosphorylation. Further, it attenuates cardiac differentiation on the one hand, and on the other hand, it directs mESC into neural fate.https://www.mdpi.com/1422-0067/22/18/9981nitro-oleic acidpluripotencymouse embryonic stem cellsSTAT3neurogenesiscardiomyogenesis |
| spellingShingle | Jana Pereckova Michaela Pekarova Nikoletta Szamecova Zuzana Hoferova Kristyna Kamarytova Martin Falk Tomas Perecko Nitro-Oleic Acid Inhibits Stemness Maintenance and Enhances Neural Differentiation of Mouse Embryonic Stem Cells via STAT3 Signaling International Journal of Molecular Sciences nitro-oleic acid pluripotency mouse embryonic stem cells STAT3 neurogenesis cardiomyogenesis |
| title | Nitro-Oleic Acid Inhibits Stemness Maintenance and Enhances Neural Differentiation of Mouse Embryonic Stem Cells via STAT3 Signaling |
| title_full | Nitro-Oleic Acid Inhibits Stemness Maintenance and Enhances Neural Differentiation of Mouse Embryonic Stem Cells via STAT3 Signaling |
| title_fullStr | Nitro-Oleic Acid Inhibits Stemness Maintenance and Enhances Neural Differentiation of Mouse Embryonic Stem Cells via STAT3 Signaling |
| title_full_unstemmed | Nitro-Oleic Acid Inhibits Stemness Maintenance and Enhances Neural Differentiation of Mouse Embryonic Stem Cells via STAT3 Signaling |
| title_short | Nitro-Oleic Acid Inhibits Stemness Maintenance and Enhances Neural Differentiation of Mouse Embryonic Stem Cells via STAT3 Signaling |
| title_sort | nitro oleic acid inhibits stemness maintenance and enhances neural differentiation of mouse embryonic stem cells via stat3 signaling |
| topic | nitro-oleic acid pluripotency mouse embryonic stem cells STAT3 neurogenesis cardiomyogenesis |
| url | https://www.mdpi.com/1422-0067/22/18/9981 |
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