PUBLICATION
Nicotinamide promotes cardiomyocyte derivation and survival through kinase inhibition in human pluripotent stem cells
- Authors
- Meng, Y., Song, C., Ren, Z., Li, X., Yang, X., Ai, N., Yang, Y., Wang, D., Zhan, M., Wang, J., Lei, C.L., Liu, W., Ge, W., Lu, L., Chen, G.
- ID
- ZDB-PUB-220326-26
- Date
- 2021
- Source
- Cell Death & Disease 12: 1119 (Journal)
- Registered Authors
- Ai, Nana, Ge, Wei
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Differentiation
- Female
- Humans
- Myocytes, Cardiac/drug effects*
- Niacinamide/pharmacology
- Niacinamide/therapeutic use*
- Phosphotransferases/antagonists & inhibitors*
- Pluripotent Stem Cells/metabolism*
- Regenerative Medicine/methods*
- Vitamin B Complex/pharmacology
- Vitamin B Complex/therapeutic use*
- Zebrafish
- PubMed
- 34845199 Full text @ Cell Death Dis.
Citation
Meng, Y., Song, C., Ren, Z., Li, X., Yang, X., Ai, N., Yang, Y., Wang, D., Zhan, M., Wang, J., Lei, C.L., Liu, W., Ge, W., Lu, L., Chen, G. (2021) Nicotinamide promotes cardiomyocyte derivation and survival through kinase inhibition in human pluripotent stem cells. Cell Death & Disease. 12:1119.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping