Third, the differentiation propensity and methylation profile of iPSC can be reset. When blood-deficient neural progenitor-derived iPSC (NP-iPSC) are differentiated into blood and then reprogrammed to pluripotency, their blood-forming potential is markedly increased. Alternatively, treatment of NP-iPSC with chromatin-modifying compounds increases blood-forming potential and is associated with reduced methylation at hematopoietic loci. For some applications, epigenetic memory of the donor cell may be advantageous, as directed differentiation to specific tissue fates remains a challenge.