Reprogramming mature terminally differentiated adipocytes to induced pluripotent stem cells

Mature adipocytes are terminally differentiated somatic cells. Here, we report the successful generation of induced pluripotent stem(i PS) cells from mouse mature adipocytes by forced expression of six transcription factors(Oct4, Sox2, c-Myc, Klf4, Rarc, and Lrh1) with a piggy Bac transposon-based strategy. The resulting i PS cells were pluripotent as evidenced by the fact that they stained positive for alkaline phosphatase, expressed high levels of key pluripotency markers including Oct4, Nanog, and SSEA1,and remained pluripotent on a 2i media. In vitro differentiation of the i PS cells showed that the cell derivatives of all three germ layers could be readily obtained through formation of embryoid bodies. Most importantly, these adipocytederived i PS cells were capable of producing chimera with high frequencies when reintroduced into early-stage embryos and transmitted through the germ line. This study demonstrates that the new six-factor reprogramming technology facilitates the reset of the terminally differentiated adipocytes to the ground state of pluripotency, enabling us to fully explore the potential of mature adipocytes as a viable cell source for regenerative medicine.

Mature adipocytes are terminally differentiated somatic cells. Here, we report the successful generation of induced pluripotent stem （iPS） cells from mouse mature adipocytes by forced expression of six transcription factors （Oct4, Sox2, c-Myc, Klf4, Rarγ, and Lrh1） with a piggyBac transposon-based strategy. The resulting iPS cells were pluripotent as evidenced by the fact that they stained positive for alkaline phosphatase, expressed high levels of key pluripotency markers including Oct4, Nanog, and SSEA1, and remained pluripotent on a 2i media. In vitro differen- tiation of the iPS cells showed that the cell derivatives of all three germ layers could be readily obtained through forma- tion of embryoid bodies. Most importantly, these adipocyte- derived iPS cells were capable of producing chimera with high frequencies when reintroduced into early-stage em- bryos and transmitted through the germ line. This study demonstrates that the new six-factor reprogramming tech- nology facilitates the reset of the terminally differentiated adipocytes to the ground state of pluripotency, enabling us to fully explore the potential of mature adipocytes as a viable cell source for regenerative medicine.