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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Temporal enhancer profiling of parallel lineages identifies AHR and GLIS1 as regulators of mesenchymal multipotency

ABSTRACT: Temporal data on gene expression and context-specific open chromatin states can improve identification of key transcription factors (TFs) and the gene regulatory networks (GRNs) controlling cellular differentiation. However, their integration remains challenging. Here, we delineate a general approach for data-driven and unbiased identification of key TFs and dynamic GRNs, called EPIC-DREM. We generated time-series transcriptomic and epigenomic profiles during differentiation of mouse multipotent bone marrow stromal cells (MSCs) towards adipocytes and osteoblasts. Using our novel approach we constructed time-resolved GRNs for both lineages and identifed the shared TFs involved in both differentiation processes. To take an alternative approach to prioritize the identified shared regulators, we mapped dynamic super-enhancers in both lineages and associated them to target genes with correlated expression profiles. The combination of the two approaches identified aryl hydrocarbon receptor (AHR) and Glis family zinc finger 1 (GLIS1) as mesenchymal key TFs controlled by dynamic MSC-specific super-enhancers that become repressed in both lineages. AHR and GLIS1 control differentiation-induced genes and we propose they function as guardians of mesenchymal multipotency.

INSTRUMENT(S): NextSeq 500, Illumina HiSeq 2000

ORGANISM(S): Mus musculus

SUBMITTER: Aurelien Ginolhac

PROVIDER: E-MTAB-6840 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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