MINDY1 is a downstream target of the polyamines and promotes embryonic stem cell self‐renewal

Embryonic stem cells have the ability to self‐renew or differentiate and these processes are under tight control. We previously reported that the polyamine regulator AMD1 is critical for embryonic stem cell self‐renewal. The polyamines putrescine, spermidine, and spermine are essential organic cations that play a role in a wide array of cellular processes. Here, we explore the essential role of the polyamines in the promotion of self‐renewal and identify a new stem cell regulator that acts downstream of the polyamines: MINDY1. MINDY1 protein levels are high in embryonic stem cells (ESCs) and are dependent on high polyamine levels. Overexpression of MINDY1 can promote ESC self‐renewal in the absence of the usually essential cytokine Leukemia Inhibitory Factor (LIF). MINDY1 protein is prenylated and this modification is required for its ability to promote self‐renewal. We go on to show that Mindy1 RNA is targeted for repression by mir‐710 during Neural Precursor cell differentiation. Taken together, these data demonstrate that high polyamine levels are required for ESC self‐renewal and that they function, in part, through promotion of high MINDY1 levels.ASTAR (Agency for Sci., Tech. and Research, S’pore)NMRC (Natl Medical Research Council, S’pore)Published versio