Our recent work spear-headed by Alexander Rauch is now published online in Nature Genetics. We have performed comprehensive characterization of the transcriptional and epigenomic changes associated with osteoblast and adipocyte differentiation of human MSC. We demonstrate that adipogenesis is driven by considerable remodeling of the chromatin landscape and de novo activation of enhancers, while osteogenesis involves activation of pre-established enhancers. Using machine learning algorithms for in silico modeling of transcriptional regulation we identify a large and diverse transcriptional network of pro-osteogenic and anti-adipogenic transcription factors. Intriguingly, binding motifs of these factors overlap with single nucleotide polymorphisms related to bone and fat formation in humans, and knockdown of single members of this network is sufficient to modulate differentiation in both directions, indicating that lineage-determination is a delicate balance between activities of many different transcription factors. The work is partly funded by DNRF141.
