EOFAD-causing mutations in psen1 orchestrate dedifferentiation through remodeling of the chromatin landscape in hiPSC-derived neurons [RNA-Seq]

In this work, we used an integrative, multi-omics approach and systems-level analysis to generate a mechanistic disease model for EOFAD in an hiPSC-derived neuron model system. hiPSC-derived neurons were generated from patient-specific Non-Demented Control, PSEN1M146L, PSEN1H163R, PSEN1A246E, and PSEN1A431E fibroblasts and subjected to RNA-Seq, ATAC-Seq, and histone methylation ChiP-Seq. For RNA-Seq, total RNA was extracted from NDC (n = 8), PSEN1M146L (n = 4), PSEN1H163R (n = 3), PSEN1A246E (n = 4), and PSEN1A431E (n = 3) hiPSC-derived neurons; libraries were generated using the Illumina RiboZero RNA prep and TrueSeq Stranded RNA library kits followed by sequencing on an Illumina HiSeq4000 generating Paired End, 100bp reads with an average of 25 million reads per sample.