Anne-Mari Håkelien

Transcriptional and epigenetic characterization of osteogenic differentiation

The project aims to characterize transcriptional and epigenetic changes during osteogenic differentiation of mesenchymal stem cells (MSCs) in order to identify regulatory networks governing bone formation. This knowledge is important in order to better understand the biology of osteosarcomas, malignant tumors of bone. For this purpose are using an immortalized MSC cell line that can be induced to differentiate to the osteogenic lineage. Using high-throughput technology we have identified subsets of transcripts that are up- or downregulated during osteogenic differentiation. We have also characterized genome-wide changes in chromatin structure using ChIP-seq with antibodies against histone H3 modifications. An example of ChIP-seq profiles for H3K4m3 (green) and H3K36m3 (blue), markers of actively transcribed genes, in undifferentiated MSCs are shown below. In addition we are also profiling changes in DNA methylation. By integration of transcription and epigenetic data we aim to gain better understanding of the molecular processes governing osteogenic differentiation.

ChIP-Seq of H3K4me3 and H3K36me3 in iMSCs