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Nicotinamide promotes cardiomyocyte derivation and survival through kinase inhibition in human pluripotent stem cells
Meng, Ya1; Song, Chengcheng2,3; Ren, Zhili2,3; Li, Xiaohong4; Yang, Xiangyu5; Ai, Nana2,3; Yang, Yang2,3; Wang, Dongjin6; Zhan, Meixiao1; Wang, Jiaxian7; Lei, Chon Lok2; Liu, Weiwei2,8; Ge, Wei2,3; Lu, Ligong1; Chen, Guokai2,3,9
2021-12-01
Source PublicationCell Death and Disease
ISSN2041-4889
Volume12Issue:12
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.

DOI10.1038/s41419-021-04395-z
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000723675200005
Scopus ID2-s2.0-85120064989
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Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorLu, Ligong; Chen, Guokai
Affiliation1.Zhuhai Precision Medical Center, Zhuhai People’s Hospital (Zhuhai hospital affiliated with Jinan University), Zhuhai, 519000, China
2.Faculty of Health Sciences, University of Macau, Taipa, Macao
3.Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Taipa, Macao
4.Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510000, China
5.School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China
6.Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210000, China
7.HELP Stem Cell Innovations Ltd. Co, Nanjing, 210000, China
8.Bioimaging and Stem Cell Core Facility, Faculty of Health Sciences, University of Macau, Taipa, Macao
9.MoE Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macao
Corresponding Author AffilicationFaculty of Health Sciences;  Centre of Reproduction, Development and Aging;  University of Macau
Recommended Citation
GB/T 7714
Meng, Ya,Song, Chengcheng,Ren, Zhili,et al. Nicotinamide promotes cardiomyocyte derivation and survival through kinase inhibition in human pluripotent stem cells[J]. Cell Death and Disease,2021,12(12).
APA Meng, Ya,Song, Chengcheng,Ren, Zhili,Li, Xiaohong,Yang, Xiangyu,Ai, Nana,Yang, Yang,Wang, Dongjin,Zhan, Meixiao,Wang, Jiaxian,Lei, Chon Lok,Liu, Weiwei,Ge, Wei,Lu, Ligong,&Chen, Guokai.(2021).Nicotinamide promotes cardiomyocyte derivation and survival through kinase inhibition in human pluripotent stem cells.Cell Death and Disease,12(12).
MLA Meng, Ya,et al."Nicotinamide promotes cardiomyocyte derivation and survival through kinase inhibition in human pluripotent stem cells".Cell Death and Disease 12.12(2021).
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