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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE113253 | GEO | 2018/12/01

REPOSITORIES: GEO

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