The same set of genetic code can be read and interpreted differently, giving rise to the variety of differentiated cell types in a multicellular organism. This principle is best illustrated by the landmark discovery by Yamanaka and colleagues, in which they demonstrated that differentiated cells such as mouse embryonic fibroblasts (MEFs) can be reprogrammed into induced pluripotent stem cells (iPSCs) following the expression of four transcription factors Oct4, Sox2, Klf4 and c-Myc. These iPSCs can give rise to all cell types including the germlines. Following this initial discovery in 2006, many researchers used similar approaches expressing different combinations of transcription factors, to derive a large variety of cell types including those of therapeutic values (neurons, cardiomyocytes, beta cells and more). Although most of these derivation processes are of low efficiency and the resulted cellular products are functionally inferior than their in vivo counterparts, the success in these processes offers the promise that any given cell type can be derived from an existing cell type from the same animal, if we know the rules how cell fate is controlled and altered.
The long term goal of our research is to deduce the set of rules of cell fate control. We use three biological model systems to investigate this question. 1) Induced pluripotency (Yamanaka reprogramming). 2) Malignant transformation. 3) Hematopoietic stem cell fate choices. We wish to use the knowledge of this set of rules to help create desired cell types for cell replacement therapies and to eliminate the emergence of harmful cell types such as cancer.