Turning Embryonic Cells into Adult Cells and All the Way Back Again
Konrad Hochedlinger, Massachusetts General Hospital

Mammalian development has been thought to be a one-way process, which starts with a few embryonic founder cells, that become more and more restricted and ultimately give rise to all specialized cell types of the body. The cloning of the sheep Dolly from an adult mammary gland cell has refuted this dogma and demonstrated that the developmental clock of a mature cell can be reset, or “reprogrammed” by the egg into that of an embryonic cell, which can support development of a copy of the donor animal. Reprogramming research has therapeutic potential in humans as it may allow for the derivation of embryonic cells from patients’ cells suffering from degenerative disorders such as Alzheimer’s disease, Parkinson’s disease or diabetes; because embryonic cells have the ability to give rise to all cell types of the body when exposed to the right combination of growth factors, these cells may provide a unique source of replacement tissue for regenerative medicine. To achieve this goal, we are studying the molecular mechanism underlying reprogramming using numerous approaches that will be discussed in the talk. For example, we use cloning, or nuclear transfer, to identify factors that might mediate reprogramming, and test their function by activating or deleting them from cells. Ultimately, our work is aimed at defining the exact sequence of molecular events that occur during reprogramming with the goal to recapitulate this process in a Petri dish without the use of eggs.

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