Abstract

Embryonic stem cells (ESCs) exhibit a striking ability to replicate continuously in the absence of senescence. Despite the knowledge gained into ESC biology and cell reprogramming, the mechanisms that regulate their pluripotency, self-renewal, and differentiation remain largely unknown. Recently, cumulative evidence has highlighted the importance of protein homeostasis, or proteostasis, in the maintenance of ESC function. These findings indicate that ESCs exhibit intrinsic differences in the regulation and activity of key nodes of the proteostasis network such as global protein synthesis, folding, and degradation rates. Here, we review new insights into proteostasis of ESCs and the questions raised by these findings. In addition, we discuss the potential of these discoveries to be applied into aging and cancer research.