상세 정보

underline
Metadata Downloads : dc(xml) or Excel
Cited 0 time in scopus ci

Title 

Nicotinamide overcomes pluripotency deficits and reprogramming barriers

Authors 

Myung Jin SonMi Young SonBinna SeolMin-Jeong KimChae Wha YooM K HanYee Sook Cho

Publisher 

Wiley-Blackwell

Issue Date 

2013

Citation 

Stem Cells, vol. 31, no. 6, pp. 1121-1135

Keywords 

Human embryonic stem cellHuman induced pluripotent stem cellNAD+NicotinamidePluripotencyReprogramming

Abstract 

Crosstalk between intracellular signaling pathways has been extensively studied to understand the pluripotency of human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells (hiPSCs); however, the contribution of NAD+-dependent pathways remains largely unknown. Here, we show that NAD+ depletion by FK866 (a potent inhibitor of NAD+ biosynthesis) was fatal in hPSCs, particularly when deriving pluripotent cells from somatic cells and maintaining pluripotency. NAD and its precursors (nicotinamide [NAM] and nicotinic acid) fully replenished the NAD+ depletion by FK866 in hPSCs. However, only NAM effectively enhanced the reprogramming efficiency and kinetics of hiPSC generation and was also significantly advantageous for the maintenance of undifferentiated hPSCs. Our molecular and functional studies reveal that NAM lowers the barriers to reprogramming by accelerating cell proliferation and protecting cells from apoptosis and senescence by alleviating oxidative stress, reactive oxygen species accumulation, and subsequent mitochondrial membrane potential collapse. We provide evidence that the positive effects of NAM (occurring at concentrations well above the physiological range) on pluripotency control are molecularly associated with the repression of p53, p21, and p16. Our findings establish that adequate intracellular NAD+ content is crucial for pluripotency; the distinct effects of NAM on pluripotency may be dependent not only on its metabolic advantage as a NAD+ precursor but also on the ability of NAM to enhance resistance to cellular stress.

ISSN 

1066-5099

Link 

http://dx.doi.org/10.1002/stem.1368

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


There are no files associated with this item.
qrcode

FusionCharts.
DSpace Software Coptright(c) 2010 MIT and Hewleft-Packard  /  KRIBB-REPOSITORY ( Email:jakim@kribb.re.kr)