GSE210107 Differentiation of human cardiomyocyte and thymic epithelial cells from H1 control hESCs and H1 hESCs uniquely modified to be DNA methylated at the promoter CpG island of MLH1.

Contributor : Joshua TompkinsSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensEngineering Pluripotent DNA Methylation by CpG Island Methylation Response (CIMR) to Synthetic CpG-free ssDNA InsertionCellular differentiation requires global changes to DNA methylation (DNAme), where it functions to regulate transcription factor and chromatin remodeling activity, and genome interpretation. Here, we describe a simple DNAme engineering approach in pluripotent stem cells (PSCs), extending across large stretches of CpG dense “islands (CGIs).” Integration of synthetic CpG free single-stranded DNA (ssDNA) induces a target CpG Island Methylation Response (CIMR) in multiple PSC lines, Nt2d1 embryonal carcinoma cells, and mouse PSCs, but not in highly methylated CpG Island Methylator Phenotype (CIMP) positive cancer l ines. CIMR DNAme at MLH1 spans the CGI, is robustly maintained throughout cellular differentiation, suppresses target gene activity, and sensitizes derived cardiomyocytes and thymic epithelial cells to the chemotherapy cisplatin. Additional CIMR DNAme is reported on at TP53 and ONECUT1 CGIs. Col lectively, this new resource enables total CpG Island DNAme engineering in pluripotency and the genesis of novel epigenetic models of development and disease
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research