Highly optimized differentiation systems of human embryonic stem cells  (hESCs)  allow derivation of distinct cell types and their intermediate stages of differentiation. 

In our lab, we exploit these differentiation systems to model human development and characterize the establishment of the RT programs in coordination with the differential gene expression patterns and remodeling of large-scale chromosome organization.

RT is also cell type-specific and can be exploited to identify developmental lineages. In fact, clustering analysis of  genome-wide RT programs from distinct cell types identify groups of cell types according to their developmental origin.

Around half of the genome changes RT during cell differentiation. These changes in RT are coordinated with transcription activity and nuclear re-localization.

Distinct genes change RT, transcriptional activity and nuclear positioning during development. For example, pluripotency-associated genes are active in stem cells, replicate early and localize at the nuclear interior. As the cells differentiate and lose pluripotency, these genes become repressed in coordination with a change to late replication and re-localization towards the nuclear periphery.

In contrast, genes required for downstream stages of cell differentiation are usually late replicating, repressed and close to the nuclear periphery in stem cells. However, as cells differentiate changes to early replication and re-localization to the nuclear interior occur in coordination with the gene activation.