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Induced human forebrain neurons overexpressing MAPT demonstrate chromatin structure alterations

ABSTRACT: We assessed whether forebrain neurons from human induced pluripotent stem cells (iNs) could recapitulate the tau-related epigenomic changes that we found in human brain H3K9ac data (Synapse ID: syn4896408). We used an existing iN model system whereby we can virally transduce NGN2-induced neurons with lentivirus to modulate expression of specific genes. Here, we overexpressed the 4R isoform of human MAPT, which induces AD-related features such as the intracellular accumulation of phosphorylated tau. To characterize the epigenomic changes in our model system, we used the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) to map genome accessibility. Finally, we utilized the iN model system to assess whether a drug compound (17-DMAG) might attenuate the tau effect on chromatin organization.

ORGANISM(S): Homo sapiens

PROVIDER: GSE97409 | GEO | 2018/12/07

REPOSITORIES: GEO

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