Epigenetic and genetic programs of mesenchymal stem cell differentiation: a genome-wide integrative approach

The progression from a stem cell state to a more differentiated progeny is determined by the specific activation of transcriptional programs, as a consequence of orchestrated epigenetic and genetic events. The current application aims to identify and char acterise transcriptional programs active during osteogenic differentiation of mesenchymal stem cells. This information will help to better understand the balance between stemness and differentiation. Using a telomerase immortalised bone marrow derived mes enchymal stem cell line model, cells will be differentiated towards the osteogenic lineage. Genome-wide changes in chromatin structure, DNA methylation and expression will be monitored during differentiation. To understand the stemness and differentiatio n process at the molecular and cellular level, the different types of data will be integrated to identify set of genes differentially expressed during differentiation, as well as transcriptional networks that are activated and silenced. By incorporating g enome-wide epigenomic information we will determine the regulation of the different networks. The information gathered from osteogenic differentiation will be compared to transcriptional networks active in malignant tumours of bone. In addition, by identi fying set of genes differentially regulated at different stages of differentiation, we will try to molecularly categorise osteosarcomas based on their differentiation stage. Using a genome-wide integrative approach, we aim to better understand transcrip tional networks in mesenchymal stem cell biology, differentiation and malignant transformation of bone.