Nicotinamide promotes cardiomyocyte derivation and survival through kinase inhibition in human pluripotent stem cells
Abstract Nicotinamide, the amide form of Vitamin B3, is a common nutrient supplement that plays important role in human fetal development. Nicotinamide has been widely used in clinical treatments, including the treatment of diseases during pregnancy. However, its impacts during embryogenesis have no...
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Nature Publishing Group
2021
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oai:doaj.org-article:2b84dabf091b4432a2db6212511358892021-12-05T12:04:31ZNicotinamide promotes cardiomyocyte derivation and survival through kinase inhibition in human pluripotent stem cells10.1038/s41419-021-04395-z2041-4889https://doaj.org/article/2b84dabf091b4432a2db6212511358892021-11-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04395-zhttps://doaj.org/toc/2041-4889Abstract Nicotinamide, the amide form of Vitamin B3, is a common nutrient supplement that plays important role in human fetal development. Nicotinamide has been widely used in clinical treatments, including the treatment of diseases during pregnancy. However, its impacts during embryogenesis have not been fully understood. In this study, we show that nicotinamide plays multiplex roles in mesoderm differentiation of human embryonic stem cells (hESCs). Nicotinamide promotes cardiomyocyte fate from mesoderm progenitor cells, and suppresses the emergence of other cell types. Independent of its functions in PARP and Sirtuin pathways, nicotinamide modulates differentiation through kinase inhibition. A KINOMEscan assay identifies 14 novel nicotinamide targets among 468 kinase candidates. We demonstrate that nicotinamide promotes cardiomyocyte differentiation through p38 MAP kinase inhibition. Furthermore, we show that nicotinamide enhances cardiomyocyte survival as a Rho-associated protein kinase (ROCK) inhibitor. This study reveals nicotinamide as a pleiotropic molecule that promotes the derivation and survival of cardiomyocytes, and it could become a useful tool for cardiomyocyte production for regenerative medicine. It also provides a theoretical foundation for physicians when nicotinamide is considered for treatments for pregnant women.Ya MengChengcheng SongZhili RenXiaohong LiXiangyu YangNana AiYang YangDongjin WangMeixiao ZhanJiaxian WangChon Lok LEIWeiwei LiuWei GeLigong LuGuokai ChenNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 12, Pp 1-13 (2021) |
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Cytology QH573-671 |
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Cytology QH573-671 Ya Meng Chengcheng Song Zhili Ren Xiaohong Li Xiangyu Yang Nana Ai Yang Yang Dongjin Wang Meixiao Zhan Jiaxian Wang Chon Lok LEI Weiwei Liu Wei Ge Ligong Lu Guokai Chen Nicotinamide promotes cardiomyocyte derivation and survival through kinase inhibition in human pluripotent stem cells |
| description |
Abstract Nicotinamide, the amide form of Vitamin B3, is a common nutrient supplement that plays important role in human fetal development. Nicotinamide has been widely used in clinical treatments, including the treatment of diseases during pregnancy. However, its impacts during embryogenesis have not been fully understood. In this study, we show that nicotinamide plays multiplex roles in mesoderm differentiation of human embryonic stem cells (hESCs). Nicotinamide promotes cardiomyocyte fate from mesoderm progenitor cells, and suppresses the emergence of other cell types. Independent of its functions in PARP and Sirtuin pathways, nicotinamide modulates differentiation through kinase inhibition. A KINOMEscan assay identifies 14 novel nicotinamide targets among 468 kinase candidates. We demonstrate that nicotinamide promotes cardiomyocyte differentiation through p38 MAP kinase inhibition. Furthermore, we show that nicotinamide enhances cardiomyocyte survival as a Rho-associated protein kinase (ROCK) inhibitor. This study reveals nicotinamide as a pleiotropic molecule that promotes the derivation and survival of cardiomyocytes, and it could become a useful tool for cardiomyocyte production for regenerative medicine. It also provides a theoretical foundation for physicians when nicotinamide is considered for treatments for pregnant women. |
| format |
article |
| author |
Ya Meng Chengcheng Song Zhili Ren Xiaohong Li Xiangyu Yang Nana Ai Yang Yang Dongjin Wang Meixiao Zhan Jiaxian Wang Chon Lok LEI Weiwei Liu Wei Ge Ligong Lu Guokai Chen |
| author_facet |
Ya Meng Chengcheng Song Zhili Ren Xiaohong Li Xiangyu Yang Nana Ai Yang Yang Dongjin Wang Meixiao Zhan Jiaxian Wang Chon Lok LEI Weiwei Liu Wei Ge Ligong Lu Guokai Chen |
| author_sort |
Ya Meng |
| title |
Nicotinamide promotes cardiomyocyte derivation and survival through kinase inhibition in human pluripotent stem cells |
| title_short |
Nicotinamide promotes cardiomyocyte derivation and survival through kinase inhibition in human pluripotent stem cells |
| title_full |
Nicotinamide promotes cardiomyocyte derivation and survival through kinase inhibition in human pluripotent stem cells |
| title_fullStr |
Nicotinamide promotes cardiomyocyte derivation and survival through kinase inhibition in human pluripotent stem cells |
| title_full_unstemmed |
Nicotinamide promotes cardiomyocyte derivation and survival through kinase inhibition in human pluripotent stem cells |
| title_sort |
nicotinamide promotes cardiomyocyte derivation and survival through kinase inhibition in human pluripotent stem cells |
| publisher |
Nature Publishing Group |
| publishDate |
2021 |
| url |
https://doaj.org/article/2b84dabf091b4432a2db621251135889 |
| work_keys_str_mv |
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1718372244304953344 |