Experimental reprogramming - induced pluripotent cells

The third lecture focused on induced pluripotent cells (iPS). Shinya Yamanaka's experiments leading to iPS cells were described in detail, as well as the experimental and ethical implications of using these cells, with an emphasis on their potential for studying differentiation processes and/or as a clinical/therapeutic tool. A large part of the lecture was devoted to the notion of "pluripotency" and how to define this state in ES and iPS cells. For murine ES and iPS cells, pluripotency is defined by their ability, when injected into a blastocyst, to develop a chimeric embryo. In humans, for ethical reasons, the same demonstrations are impossible, and the criterion of pluripotency retained is the ability of ES and iPS cells to induce the formation of teratomas (derived from the three embryonic tissues) when injected under the skin of immunodeficient mice. Shinya Yamanaka and colleagues have shown that the pluripotency state depends on the expression of various transcription factors (OCT4, SOX2, NANOG, SALL4...), as well as on a particular chromatin conformation. Nevertheless, the reprogramming process is still far from being understood, and the genetic and epigenetic bases are the subject of active research, discussed in the fourth lecture. The differentiation of iPS cells into different lineages using specific factors is now also possible, and in an increasingly controlled way. Therapeutic prospects therefore seem relatively close, even if a number of problems remain, which we described in the fifth lecture.