Nicotinamide Promotes Cell Survival and Differentiation as Kinase Inhibitor in Human Pluripotent Stem Cells

被引:76
作者
Meng, Ya [1 ,2 ]
Ren, Zhili [1 ]
Xu, Faxiang [1 ]
Zhou, Xiaoxiao [1 ]
Song, Chengcheng [1 ]
Wang, Vivien Ya-Fan [2 ,3 ]
Liu, Weiwei [1 ,4 ]
Lu, Ligong [5 ]
Thomson, James A. [6 ,7 ]
Chen, Guokai [1 ,2 ]
机构
[1] Univ Macau, Ctr Reprod Dev & Aging, Fac Hlth Sci, Taipa, Macau, Peoples R China
[2] Univ Macau, Inst Translat Med, Fac Hlth Sci, Taipa, Macau, Peoples R China
[3] Univ Macau, Ctr Canc, Fac Hlth Sci, Taipa, Macau, Peoples R China
[4] Univ Macau, Bioimaging & Stem Cell Core Facil, Fac Hlth Sci, Taipa, Macau, Peoples R China
[5] Jinan Univ, Zhuhai Peoples Hosp, Ctr Intervent Radiol, Zhuhai Precis Med Ctr, Zhuhai 519000, Guangdong, Peoples R China
[6] Morgridge Inst Res, Regenerat Biol, Madison, WI 53715 USA
[7] Univ Wisconsin, Dept Cell & Regenerat Biol, Madison, WI 53706 USA
关键词
IN-VITRO EXPANSION; DIRECTED DIFFERENTIATION; INDUCED APOPTOSIS; PROGENITOR CELLS; BETA-CATENIN; PHOSPHORYLATION; PREVENTION; ORGANOIDS; MECHANISM; PATHWAYS;
D O I
10.1016/j.stemcr.2018.10.023
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Nicotinamide, the amide form of vitamin B3, is widely used in disease treatments and stem cell applications. However, nicotinamide's impact often cannot be attributed to its nutritional functions. In a vitamin screen, we find that nicotinamide promotes cell survival and differentiation in human pluripotent stem cells. Nicotinamide inhibits the phosphorylation of myosin light chain, suppresses actomyosin contraction, and leads to improved cell survival after individualization. Further analysis demonstrates that nicotinamide is an inhibitor of multiple kinases, including ROCK and casein kinase 1. We demonstrate that nicotinamide affects human embryonic stem cell pluripotency and differentiation as a selective kinase inhibitor. The findings in this report may help researchers design better strategies to develop nicotinamide-related stem cell applications and disease treatments.
引用
收藏
页码:1347 / 1356
页数:10
相关论文
共 56 条
[1]   High-dose B vitamin supplementation and cognitive decline in Alzheimer disease - A randomized controlled trial [J].
Aisen, Paul S. ;
Schneider, Lon S. ;
Sano, Mary ;
Diaz-Arrastia, Ramon ;
van Dyck, Christopher H. ;
Weiner, Myron F. ;
Bottiglieri, Teodoro ;
Jin, Shelia ;
Stokes, Karen T. ;
Thomas, Ronald G. ;
Thal, Leon J. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2008, 300 (15) :1774-1783
[2]   Axin-mediated CKI phosphorylation of β-catenin at Ser 45:: a molecular switch for the Wnt pathway [J].
Amit, S ;
Hatzubai, A ;
Birman, Y ;
Andersen, JS ;
Ben-Shushan, E ;
Mann, M ;
Ben-Neriah, Y ;
Alkalay, I .
GENES & DEVELOPMENT, 2002, 16 (09) :1066-1076
[3]   Mechanism of sirtuin inhibition by nicotinamide:: Altering the NAD+ cosubstrate specificity of a Sir2 enzyme [J].
Avalos, JL ;
Bever, KM ;
Wolberger, C .
MOLECULAR CELL, 2005, 17 (06) :855-868
[4]   Nicotinamide yields impressive results in skin cancer [J].
Bagcchi, Sanjeet .
LANCET ONCOLOGY, 2015, 16 (16) :E591-E591
[5]   Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells [J].
Blaschke, Kathryn ;
Ebata, Kevin T. ;
Karimi, Mohammad M. ;
Zepeda-Martinez, Jorge A. ;
Goyal, Preeti ;
Mahapatra, Sahasransu ;
Tam, Angela ;
Laird, Diana J. ;
Hirst, Martin ;
Rao, Anjana ;
Lorincz, Matthew C. ;
Ramalho-Santos, Miguel .
NATURE, 2013, 500 (7461) :222-+
[6]   Rapid and Efficient Directed Differentiation of Human Pluripotent Stem Cells Into Retinal Pigmented Epithelium [J].
Buchholz, David E. ;
Pennington, Britney O. ;
Croze, Roxanne H. ;
Hinman, Cassidy R. ;
Coffey, Peter J. ;
Clegg, Dennis O. .
STEM CELLS TRANSLATIONAL MEDICINE, 2013, 2 (05) :384-393
[7]   NICOTINAMIDE AND PREVENTION OF DIABETES [J].
CHASE, P ;
DUPRE, J ;
MAHON, J ;
EHRLICH, R ;
GALE, E ;
KOLB, H ;
LAMPETER, E ;
NERUP, J .
LANCET, 1992, 339 (8800) :1051-1052
[8]   A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention [J].
Chen, Andrew C. ;
Martin, Andrew J. ;
Choy, Bonita ;
Fernandez-Penas, Pablo ;
Dalziell, Robyn A. ;
McKenzie, Catriona A. ;
Scolyer, Richard A. ;
Dhillon, Haryana M. ;
Vardy, Janette L. ;
Kricker, Anne ;
St George, Gayathri ;
Chinniah, Niranthari ;
Halliday, Gary M. ;
Damian, Diona L. .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (17) :1618-1626
[9]   Actin-Myosin Contractility Is Responsible for the Reduced Viability of Dissociated Human Embryonic Stem Cells [J].
Chen, Guokai ;
Hou, Zhonggang ;
Gulbranson, Daniel R. ;
Thomson, James A. .
CELL STEM CELL, 2010, 7 (02) :240-248
[10]   Fast instance selection for speeding up support vector machines [J].
Chen, Jingnian ;
Zhang, Caiming ;
Xue, Xiaoping ;
Liu, Cheng-Lin .
KNOWLEDGE-BASED SYSTEMS, 2013, 45 :1-7