Unraveling the 2,3-diketo-l-gulonic acid-dependent and -independent impacts of l-ascorbic acid on somatic cell reprogramming
Abstract Background l-ascorbic acid (Asc) plays a pivotal role in regulating various biological processes, including somatic cell reprogramming, through multiple pathways. However, it remains unclear whether Asc regulates reprogramming directly or functions through its metabolites. Results Asc exhib...
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Cell & Bioscience |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13578-023-01160-x |
| _version_ | 1797413884604186624 |
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| author | Lining Liang Meiai He Yixin Zhang Chenchen Wang Zhaohui Qin Qian Li Tingting Yang Fei Meng Yusheng Zhou Haofei Ge Weining Song Shiyu Chen Linna Dong Qiwen Ren Changpeng Li Lin Guo Hao Sun Wei Zhang Duanqing Pei Hui Zheng |
| author_facet | Lining Liang Meiai He Yixin Zhang Chenchen Wang Zhaohui Qin Qian Li Tingting Yang Fei Meng Yusheng Zhou Haofei Ge Weining Song Shiyu Chen Linna Dong Qiwen Ren Changpeng Li Lin Guo Hao Sun Wei Zhang Duanqing Pei Hui Zheng |
| author_sort | Lining Liang |
| collection | DOAJ |
| description | Abstract Background l-ascorbic acid (Asc) plays a pivotal role in regulating various biological processes, including somatic cell reprogramming, through multiple pathways. However, it remains unclear whether Asc regulates reprogramming directly or functions through its metabolites. Results Asc exhibited dual capabilities in promoting reprogramming through both 2,3-diketo-l-gulonic acid (DKG), a key metabolite during Asc degradation, dependent and independent routes. On the one hand, Asc facilitated reprogramming by promoting cell proliferation and inducing the conversion from pre-induced pluripotent stem cells (pre-iPSCs) to iPSCs through DKG-independent pathways. Additionally, Asc triggered mesenchymal-epithelial transition (MET) and activated glycolysis via DKG-dependent mechanisms. Notably, DKG alone activated a non-canonical tricarboxylic acid cycle characterized by increased succinate, fumarate, and malate. Consequently, this shift redirected oxidative phosphorylation toward glycolysis and induced MET. Moreover, owing to its antioxidant capabilities, Asc directly inhibited glycolysis, thereby preventing positive feedback between glycolysis and epithelial-mesenchymal transition, ultimately resulting in a higher level of MET. Conclusion These findings unveil the intricate functions of Asc in the context of reprogramming. This study sheds light on the DKG-dependent and -independent activities of Asc during reprogramming, offering novel insights that may extend the application of Asc to other biological processes. |
| first_indexed | 2024-03-09T05:24:25Z |
| format | Article |
| id | doaj.art-859d569186314af5aab7ac084bad0099 |
| institution | Directory Open Access Journal |
| issn | 2045-3701 |
| language | English |
| last_indexed | 2024-03-09T05:24:25Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj.art-859d569186314af5aab7ac084bad00992023-12-03T12:37:48ZengBMCCell & Bioscience2045-37012023-11-0113111610.1186/s13578-023-01160-xUnraveling the 2,3-diketo-l-gulonic acid-dependent and -independent impacts of l-ascorbic acid on somatic cell reprogrammingLining Liang0Meiai He1Yixin Zhang2Chenchen Wang3Zhaohui Qin4Qian Li5Tingting Yang6Fei Meng7Yusheng Zhou8Haofei Ge9Weining Song10Shiyu Chen11Linna Dong12Qiwen Ren13Changpeng Li14Lin Guo15Hao Sun16Wei Zhang17Duanqing Pei18Hui Zheng19Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGuangzhou LaboratoryGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGuangzhou LaboratoryCentre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of SciencesGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesAbstract Background l-ascorbic acid (Asc) plays a pivotal role in regulating various biological processes, including somatic cell reprogramming, through multiple pathways. However, it remains unclear whether Asc regulates reprogramming directly or functions through its metabolites. Results Asc exhibited dual capabilities in promoting reprogramming through both 2,3-diketo-l-gulonic acid (DKG), a key metabolite during Asc degradation, dependent and independent routes. On the one hand, Asc facilitated reprogramming by promoting cell proliferation and inducing the conversion from pre-induced pluripotent stem cells (pre-iPSCs) to iPSCs through DKG-independent pathways. Additionally, Asc triggered mesenchymal-epithelial transition (MET) and activated glycolysis via DKG-dependent mechanisms. Notably, DKG alone activated a non-canonical tricarboxylic acid cycle characterized by increased succinate, fumarate, and malate. Consequently, this shift redirected oxidative phosphorylation toward glycolysis and induced MET. Moreover, owing to its antioxidant capabilities, Asc directly inhibited glycolysis, thereby preventing positive feedback between glycolysis and epithelial-mesenchymal transition, ultimately resulting in a higher level of MET. Conclusion These findings unveil the intricate functions of Asc in the context of reprogramming. This study sheds light on the DKG-dependent and -independent activities of Asc during reprogramming, offering novel insights that may extend the application of Asc to other biological processes.https://doi.org/10.1186/s13578-023-01160-xAscMetaboliteDKGTCA cycleMET |
| spellingShingle | Lining Liang Meiai He Yixin Zhang Chenchen Wang Zhaohui Qin Qian Li Tingting Yang Fei Meng Yusheng Zhou Haofei Ge Weining Song Shiyu Chen Linna Dong Qiwen Ren Changpeng Li Lin Guo Hao Sun Wei Zhang Duanqing Pei Hui Zheng Unraveling the 2,3-diketo-l-gulonic acid-dependent and -independent impacts of l-ascorbic acid on somatic cell reprogramming Cell & Bioscience Asc Metabolite DKG TCA cycle MET |
| title | Unraveling the 2,3-diketo-l-gulonic acid-dependent and -independent impacts of l-ascorbic acid on somatic cell reprogramming |
| title_full | Unraveling the 2,3-diketo-l-gulonic acid-dependent and -independent impacts of l-ascorbic acid on somatic cell reprogramming |
| title_fullStr | Unraveling the 2,3-diketo-l-gulonic acid-dependent and -independent impacts of l-ascorbic acid on somatic cell reprogramming |
| title_full_unstemmed | Unraveling the 2,3-diketo-l-gulonic acid-dependent and -independent impacts of l-ascorbic acid on somatic cell reprogramming |
| title_short | Unraveling the 2,3-diketo-l-gulonic acid-dependent and -independent impacts of l-ascorbic acid on somatic cell reprogramming |
| title_sort | unraveling the 2 3 diketo l gulonic acid dependent and independent impacts of l ascorbic acid on somatic cell reprogramming |
| topic | Asc Metabolite DKG TCA cycle MET |
| url | https://doi.org/10.1186/s13578-023-01160-x |
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