Rcor2, the corepressor 2 of REST, is predominantly expressed in embryonic stem cells (ESCs) and plays a crucial role in regulating ESC pluripotency, neurogenesis, and somatic cell fate determination. It is involved in various biological processes through its association with chromatin-modifying complexes and regulation of gene expression [1,2,3].

In gene knockout studies, Rcor2-/-mouse embryonic stem cells (mESCs) show reduced proliferation and severely compromised capacity to differentiate into all three germ layers. Conversely, Rcor2 knockout promotes primordial germ cells (PGCs) specific gene expression and possibly PGC formation. Mechanistically, Rcor2 inhibits expression of genes required for PGC development by associating to their promoters and enhancing local suppressive H3K9me3 modifications [1].

In addition, depletion of Rcor2 in neural stem cells in mice results in reduced neural progenitor cell (NPC) proliferation, neuron population, neocortex thickness, and brain size, suggesting its importance in cortical development [3]. Lentiviral silencing of Rcor2 in MC3T3-E1 cells led to a decrease in osteoblast differentiation in vitro, while conditional deletion of Rcor2 in limb-bud mesenchymal cells led to a moderate decrease in cortical bone volume in vivo [4].

In conclusion, Rcor2 is essential for somatic differentiation, represses germline cell fate, and is involved in neurogenesis and mesenchymal stromal cell differentiation. Gene knockout and conditional knockout mouse models have been instrumental in revealing its roles in these biological processes, which may have implications for understanding embryonic development, neurodegenerative diseases, and bone-related disorders [1,3,4].