Self-Renewal

The concept of self-renewal 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.

The lab of Steve Elledge has 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.