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Distinct Chromatin States Define a Program Of Mesenchymal Stem Cell Commitment To Osteogenesis

ABSTRACT: Multipotent mesenchymal stromal cells (MSCs) from bone marrow are critical for regeneration and homeostasis of multiple tissues. As epigenetic mechanisms are a fundamental regulator of lineage specification and cell fate, we examined histone modification changes in MSCs at distinct stages osteogenic differentiation, including: proliferation, early commitment, matrix deposition, and mineralization. Temporal changes of multiple histone modifications along with several transcriptional regulators were assessed and correlated to gene expression, which revealed distinct epigenetic mechanisms that regulate transcriptional programs necessary for commitment and tissue-specific phenotype development. Patterns of stage-specific enrichment of histone modifications revealed distinct modes of repression and activation of gene expression that would not be detected using single endpoint analysis. In addition, we have defined dynamic enhancer regions that control tissue-specific genes. Our work provides a cornerstone to understand the epigenetic regulation of transcriptional programs that are important for MSC commitment, as well as insights to facilitate MSC-based therapeutic interventions.

ORGANISM(S): Mus musculus

PROVIDER: GSE76074 | GEO | 2017/05/05

SECONDARY ACCESSION(S): PRJNA306161

REPOSITORIES: GEO

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