Reprogramming Factors in stem cells

In 2006, the Yamanaka lab identified four factors that, when co-transfected and expressed in mouse adult fibroblast cells, caused those fibroblasts to revert back to a pluripotent like state.  One year later, the same four factors were used to successfully reprogram human adult fibroblast cells into induced pluripotent stem cells.  These four factors are:

Octamer-4 (Oct-4) encoded by the gene POU5F1 is a transcription factor that is highly expressed in undifferentiated embryonic stem cells compared to other somatic cells.  Oct-4 expression in embryonic stem cells is critical to maintain them in an undifferentiated, pluripotent state.  In fact, if Oct-4 experession is experimentally knocked out, this causes embryonic stem cells to spontaneously differentiate.

SOX2 is a transcription factor critical for the maintenance of pluripotency in embryonic stem cells. SOX2 and Oct-4 work in parallel to co-regulate expression of target genes involved in the maintenance of pluripotency.

c-Myc is a well known proto-oncogene. The c-Myc gene codes for a transcription factor that regulates the expression of many genes involved in the control of cell proliferation, growth, differentiation and apoptosis. Abberant expression of c-Myc on the other hand is associated with tumor formation and cancer.  Recent studies have demonstated that c-Myc is a dispensable reprograming factor; however, the transcription factor has been shown to greatly improve reprogramming efficiency.

Kruppel-like factor 4 (Klf-4) is a transcription factor that is highly expressed in undifferentiated ES cells and is also expressed elsewhere in the adult organism including the gut, testis and lungs and functions to regulate proliferation, differentiation and cell survival.