Abstract
NF-κB signaling plays an essential role in maintaining the undifferentiated state of embryonic stem (ES) cells. However, opposing roles of NF-κB have been reported in mouse and human ES cells, and the role of NF-κB in human induced pluripotent stem (iPS) cells has not yet been clarified. Here, we report the role of NF-κB signaling in maintaining the undifferentiated state of human iPS cells. Compared with differentiated cells, undifferentiated human iPS cells showed an augmentation of NF-κB activity. During differentiation induced by the removal of feeder cells and FGF2, we observed a reduction in NF-κB activity, the expression of the undifferentiation markers Oct3/4 and Nanog, and the up-regulation of the differentiated markers WT-1 and Pax-2. The specific knockdown of NF-κB signaling using p65 siRNA also reduced the expression of Oct3/4 and Nanog and up-regulated WT-1 and Pax-2 but did not change the ES-like colony formation. Our results show that the augmentation of NF-κB signaling maintains the undifferentiated state of human iPS and suggest the importance of this signaling pathway in maintenance of human iPS cells.
Highlights
Mouse and human embryonic stem (ES) cells have differences in morphology, doubling times, and the expression of differentiation markers [1]
These results confirmed that the human induced pluripotent stem (iPS) cells used in this study (253G1) were properly re-programmed and were similar to human ES cells
Human iPS cells have great therapeutic potential, but the role of NF-kB signaling in the maintenance of their pluripotency has not been fully understood
Summary
Mouse and human embryonic stem (ES) cells have differences in morphology, doubling times, and the expression of differentiation markers [1]. Self-renewal and the undifferentiated state of mouse ES cells depend on the activation of Stat by leukemia inhibitory factor (LIF) and Bmp signaling [2,3]. Human ES cells require FGF2 signaling or ERK activation and co-operation with Activin/Nodal signaling [4], but not LIF/Stat and Bmp signaling. In 2006, Yamanaka et al established induced pluripotent stem (iPS) cells [5,6]. The function of human iPS cells and human ES cells is thought to be similar, an understanding of the molecular mechanism by which pluripotency and the undifferentiated state is maintained in human iPS cells is important for the clinical application of these cells
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