Direct Conversion of Trophoblast Stem Cells into Pluripotent Stem Cells by Oct4. Mus musculus

Embryonic stem (ES) cells and trophoblast stem (TS) cells are both derived from early embryos, yet these cells have distinct differentiation properties. ES cells can differentiate into all three germ layer cell types, whereas TS cells can only differentiate into placental cells. It has not been determined whether TS cells can be converted into ES-like pluripotent stem (PS) cells. Here we report that overexpression of a single transcription factor, Oct4, in TS cells is sufficient to convert TS cells into a pluripotent state. These Oct4 induced pluripotent stem (OiPS) cells have the epigenetic characteristics of ES cells, including X chromosome reactivation and elevated H3K27 me3 modifications. The gene expression profile of OiPS cells and ES cells was very similar. Moreover, OiPS cells can differentiate into the three germ layer cell types in vitro and in vivo. More importantly, chimeric mice with germline transmission could be efficiently produced from OiPS cells. To our knowledge, this is the first evidence showing that only one single transcription factor could convert the non-embryonic TS cells into pluripotent stem cells with pluripotency. Overall design: Gene expression profile of iPS cells and trophoblast stem cells were generated by Affymetrix Mouse Gene 1.0 ST Array. The Gene expression profile of ES cell R1 in GSE17004 was used as control. Three biological repeats were included for each line.