We have introduced 1 to 2 copies of a deletion mutant (betaDeltaC) of the human retinoic acid receptor beta into mouse embryonic stem (ES) cells. The betaDeltaC-expressing cells were 10 to 100 times less sensitive to RA-induced differentiation in comparison to their parental cells. In the presence of 10-7 M RA in monolayer culture, they showed no growth arrest or differentiation, but remained pluripotent. Embryoid Bodies (EBs) derived from betaDeltaC-expressing cells differentiated into cardiomyocytes rather than neurons after treatment with 10-6 M RA, and became neurons upon exposure to 10-5 or 10-4 M RA. Remarkably, after 10 passages of continuous culture in the presence of 10-7 M RA, they still were able to form chimeras after injection into blastocysts. These data suggest that appropriate levels of normal retinoid receptors are crucial for lineage-specific differentiation of mouse ES cells in vitro. The betaDeltaC mutant protein may prove to be useful in promoting "stemness" of ES cells in culture.
Chatzi, C., van den Brink, C. E., van der Saag, P. T., McCaig, C. D., & Shen, S. (2010). Expression of a mutant retinoic acid receptor beta alters lineage differentiation in mouse embryonic stem cells. Stem Cells and Development, 19(7), 951-960. https://doi.org/10.1089/scd.2009.0517