Osteogenesis depends on commissioning of a network of stem cell transcription factors that act as repressors of adipogenesis

Here we have used both chromatin accessibility and enhancer activity marks to study enhancer activation and changes in transcriptional networks during the differentiation of human MSC into osteoblasts and adipocytes. 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 predict the repertoire of transcription factors that drive the two differentiation pathways. We show that osteoblast differentiation depends on the activation of a large and diverse transcriptional network of pro-osteogenic and anti-adipogenic transcription factors. Intriguingly, 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. Overall design: Genome-wide profiling of chromatin accessibility and enhancer activity using H3K27ac and MED1 ChIP-seq during differentiation of human mesenchymal stem cells towards osteoblasts and adipocytes Raw data are not available for primary stromal cell samples due to patient privacy concerns. If you are interested in accessing these data, please contact the submitter directly.