Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells.

摘要

In embryonic stem cell (ESC) lines generated from human embryos determined through preimplantation genetic diagnosis to carry the fragile X mutation, the FMR1 gene is expressed in undifferenti-ated cells but undergoes transcriptional silencing after ESC differentiation (Eiges et al., 2007). Here, we generated induced pluripotent stem cell (iPSC) lines from fibroblasts of individuals carrying the fragile X mutation. Despite successful reprog-ramming of the somatic cells to pluripo-tency, the FMR1 gene remained inactive and carried DNA methylation and his-tone modifications indicative of inactive heterochromatin. These data highlight critical differences between ESCs and iPSCs in modeling fragile X disorder.Pluripotent stem cells are potentially an important tool to model human genetic disorders. Human embryonic stem cells can recapitulate early stages of human development, and they can also differentiate into cells from the three embryonic germ layers (Schuldiner et al., 2000; Thomson et al., 1998).