Undifferentiated cells in the inner cell mass (green) contain proteins damaged by carbonylation (red).


Malin Hernebring, Thomas Nyström (Göteborg University, Göteborg, Sweden), and colleagues find that mouse embryonic stem (ES) cells do some spring cleaning during differentiation to rid themselves of protein damage.

Protein damage is absent in young tissue but accumulates with age. The authors wondered what prevents run-down proteins from being passed via the germline to a newly developing organism.

To address this issue, the researchers measured carbonylation and advanced glycation end product (AGE) formation—two common types of protein damage—in cultured undifferentiated ES cells. “What's been assumed,” says Nyström, “is that the [ES] cells would be miraculously kept free of protein damage.” But the group was surprised to find levels of these contamination products equivalent to those found in a middle-aged mouse.

After cultured ES cells differentiated, levels of both damage markers dropped dramatically. In blastocysts, too, proliferating cells of the inner cell mass showed damage, but differentiated cells on the outer surface did not.

The elimination of protein damage was accompanied by a threefold increase in the activity of the 20S proteasome, which was previously implicated in degrading oxidative stress products. Nyström posits that this process cleanses the cellular protein slate. The team is now examining how the proteasome's activity is regulated.


Hernebring, M., et al.
Proc. Natl. Acad. Sci. USA.