Now queue the sound of a turntable needle ripping across a vinyl record and then drop-kick yourself into reality (Ouch!): office phone ringing, inbox bulging, the rats closing in. How grand it would be to have some of that warm sand under our feet and a more than frequent chance at self-renewal. To be able to rejuvenate ourselves at our most basic cellular presence and leave us with no worries. But as the ripping sound continues, self-renewal at that cellular level actually proceeds; but it won’t transport us to that place far away. Instead it may, just as importantly, re-populate our tissues and lead us to clues about regenerative medicine and promising cancer therapies.
The concept of self-renewal (in the geeky sense) applies to adult pluripotent stem cells as well as embryonic stem cells. Self-renewal allows a cell to maintain itself in an undifferentiated state until it receives signals to commit to a particular lineage. I might think that the people in the lab of Steve Elledge probably haven’t had a dose of that grand level of self-renewal in a long time (they appear to not be allowed to sleep… how else is it possible to publish so prolifically!). But their hard work as well as that of others has paid off and contributed to our progress of getting to the bottom of how stem cells remain pluripotent and provide a constant source of cellular self-renewal. Hu et al., of the Elledge lab at Harvard Medical School, set out to identify genes essential for self-renewal in mouse embryonic stem (ES) cells. The group approached this by carrying out a genome-wide RNAi screen in mouse cells using a functional assay that employed a very clever GFP reporter system in which GFP expression correlated with ES cell identity. This screen led to the re-identification of known and suspected ES cell self-renewal genes as well as the identification of others not yet implicated in the network. Of the over 100 newly identified factors they selected two transcriptional regulators for further investigation since knockdown led to relatively strong phenotypes. Cnot3 and Trim28/KAP-1 were the two factors investigated and found to regulate self-renewal via the modification of chromatin structure. Further studies of human Cnot3, Trim28/KAP-1 and their associated proteins will likely lead to the identification of new stem cell pathways. And perhaps when we figure it all out, we can just relax in an ocean breeze.