Human parthenogenetic stem cells produce enriched populations of definitive endoderm cells after trichostatin A pretreatment

Abstract

Human parthenogenetic stem cells (hpSC) hold great promise as a source of pluripotent stem cells for cell-based transplantation therapy due to their ethical method of derivation as well as the enhanced capacity for immunomatching with significant segments of the human population. We report here the directed differentiation of hpSC to produce enriched populations of definitive endoderm. Moreover, we find that treatment of undifferentiated hpSC by trichostatin A (TSA) before applying the directed differentiation protocol significantly increases the proportion of definitive endoderm cells in the final population. TSA-pretreated as well as non-TSA-treated hpSC undergoing differentiation toward definitive endoderm demonstrate a similar temporal sequence of gene expression to that which occurs in the course of definitive endoderm differentiation during vertebrate gastrulation and for differentiation of hESCs to definitive endoderm. Creation of the definitive endoderm lineages from hpSC represents the critical first step toward the development of hpSC-based cellular therapies for diseases of the liver or pancreas.