Genomic and epigenomic regulation of cell fate

Multicellular organisms are composed of hundreds of cells types with an identical genome. DNA is packaged in the form of “chromatin” including nucleosomes, epigenetic modifications and a large number of proteins associated with transcription, remodelling or DNA repair. In this way, genetic information is decoded differently in each cell type, leading to distinct phenotypes and specialised functions.

How is cellular identity regulated during developmental processes, or disrupted in pathological conditions? Many molecular players are known to influence cell fate decisions, such as transcription factors and epigenetic regulators. However, how these macromolecules act together on chromatin to modulate gene expression programs remains poorly understood.

In our laboratory, we exploit a combination of cutting-edge genetic engineering, biochemical assays and high-throughput sequencing technologies to dissect the molecular mechanisms of proteins associated with chromatin. These factors are critical for embryonic development and often de-regulated in human diseases such as cancer and neurodevelopmental disorders.

We take advantage of embryonic stem cells as a model system for cell fate decisions. Using genetically manipulated pluripotent cells, we can assess not only the influence of proteins of interest on the transcriptome and epigenome, but also test their phenotypic impact on cellular differentiation in vitro.