X-chromosome reactivation during stem cell reprogramming

A defining feature of X-chromosome inactivation and reactivation is their link to the differentiated and naïve pluripotent state, respectively (Figure 3). This makes it possible to study these processes outside the embryo using in vitro differentiation and dedifferentiation systems. A lot of knowledge has been gained on the X-inactivation process using the embryonic stem cell differentiation model. On the other hand, little is known about the mechanisms of X-reactivation but this is now amenable to study since in vitro systems for dedifferentiation like iPSC reprogramming have been developed.

In our laboratory we are using these in vitro approaches to complement our work on X-reactivation in mouse embryos. In particular we want to elucidate the molecular mechanisms and defining factors for X-reactivation, which are required for the process and which link it to the naïve pluripotent stem cell state.

Figure 3: The X-chromosome state in female mice is linked to cell differentiation. Pluripotent stem cells have two active X-chromosomes (XaXa) and undergo X-Chromosome Inactivation, when differentiated resulting in one active and one inactive X-Chromosome (XaXi). During reprogramming of differentiated cells, this is reversed by X-Chromosome Reactivation.