DNA methylation profiles of JAK2-derived induced pluripotent stem cells (iPSC)

Myeloproliferative neoplasms (MPN) are a clonal hematological disease which harbors different driver mutations, including JAK2 V617F, and there is clear evidence that MPN is associated with aberrant DNA methylation (DNAm). However, it is unclear whether the driver mutation alone is sufficient to recapitulate the MPN phenotype and the global DNA methylation changes observed in patients. For this purpose, we utilized three established induced pluripotent stem cell (iPSC) clones carrying the JAK2 V617F mutation, both heterozygous and homozygous genotypes along with their wild type (WT) counterparts. These iPSCs were differentiated towards hematopoietic stem and progenitor differentiation (iHPCs) to capture the mutant phenotype. Genome wide methylation analysis of JAK2 mutated iPSCs and iHPCs showed no significant methylation differences compared to wild type cells. The iPSC model only partially recapitulated the DNAm changes observed in patients with JAK2 mutation, suggesting that epigenetic changes are not directly evoked by the driver mutation, but rather accumulate over the course of disease development. We analyzed genome-wide DNA-methylation changes in JAK2 V617F in an iPSC model. Three patient derived iPSCs, each with three genotypes (wild type, JAK2 V617F heterozygous and homozygous mutation) were utilized. iPSC cells were differentiated towards hematopoietic stem and progenitor cells (iHPCs) and collected for DNA isolation.