Polycomb switch in stem cell differentiation
The cover of the January issue of the journal Cell Stem Cell highlights the article: “Nonoverlapping functions of the polycomb group Cbx family of proteins in embryonic stem cells” by Luciano Di Croce and colleagues at the CRG. Although it is known that polycomb complexes (PRC) play an important role in the regulation of embryonic stem cell (ESC) pluripotency and early developmental cell fate decisions, this research has now shown that different Cbx protein compositions of the complex can modulate this regulation.
In pluripotent cells, Cbx7 is the main PRC1-associated Cbx protein and is required to maintain the undifferentiated state in a robust manner by repressing a large number of genes involved in lineage specification. The expression of Cbx7 diminishes as ESCs differentiate, most likely due to the reduction of the transcription factor Oct4, a marker of undifferentiated cells. As a consequence, during differentiation different task-specific PRC1 complexes are formed with Cbx2, 4, 6 or 8 proteins replacing the Cbx7 protein. Cbx4, for example, regulates the epidermal stem cell differentiation.
“We discovered that implanting ESCs depleted for the different specific Cbx proteins led to mice developing tumors with different characteristics. This showed that each Cbx protein has a unique function. Even though there is no medical application at the present time, these results will surely generate research towards developing anti-tumoural drugs that could block these type of proteins”, says Di Croce.
Morey L, Pascual G, Cozzuto L, Roma G, Wutz A, Benitah SA, Di Croce L. Nonoverlapping functions of the polycomb group cbx family of proteins in embryonic stem cells. Cell Stem Cell. 2012 Jan 6;10(1):47-62