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Dissection of molecular signature transformation during the process of pluripotency induction

Final Report Summary - ROADTOIPS (Dissection of molecular signature transformation during the process of pluripotency induction)

During the process of development, whereby over 300 different cell types are generated from a single fertilized egg, cells gradually become specialized. This process had been believed to be irreversibly until very recently. In 2006, a group of scientists found that any specialized cells can become uncommitted pluripotent cells like stem cells in embryos by artificially manipulating only 4 genes simultaneously. This trick that rewound the cells’ biological time clock is called ‘reprogramming’ and the resulting artificially generated uncommitted cells are called ‘induced pluripotent stem cells (iPSCs)’. The findings brought tremendous excitement to the stem cell and medical research community. iPSCs can be generated from any cell in the body (e.g. your skin cells) and in theory can be used for the production of any desired cell types for transplantation, drug screening, toxicology tests and so forth.
However, this reprograming process is very inefficient, only 1 in 100 cells can be converted to iPSCs. The molecular mechanisms of this process is hardly known and it was also mystery if cells trace back how they became the specialized cells from the unspecialized cells or not during reprogramming. In this project we revealed that the reprogramming process is not the reversal of normal development. Specialized cells take distinct steps on the way back to an unspecialized pluripotent state. The reprogramming system we developed in this project has been further used to illuminate molecular mechanisms of reprogramming.