Reprogramming Differentiated Human Cells to a Pluripotent State

Reprogramming Differentiated Human Cells to a Pluripotent State

Funding Type: 
SEED Grant
Grant Number: 
RS1-00319
Award Value: 
$380,005
Stem Cell Use: 
Embryonic Stem Cell
iPS Cell
Cell Line Generation: 
iPS Cell
Status: 
Closed
Public Abstract: 
Statement of Benefit to California: 
Progress Report: 

Year 1

If the therapeutic potential of human embryonic stem (ES) cells is to be realized, the ability to produce pluripotent stem cells with defined genetic backgrounds is essential. Pluripotent cells, through differentiation, have the ability to become any cell type. For basic and applied research, access to human ES cells derived from patients with specific diseases would be very valuable. In a more therapeutic setting, the ability to isolate differentiated cells from an individual patient and reprogram these cells to a pluripotent, stem-like state may ultimately lead to truly personalized medicine. Thus, an understanding of the genes that establish and maintain the pluripotent state of human ES cells is critical to future medical applications. The overall goal of this research program was to establish experimental protocols to efficiently reprogram differentiated human cells into a pluripotent state. We have recently developed a new technology for regulating protein expression in human cells, and this technology allowed us to regulate the expression levels of the reprogramming proteins with excellent control. We showed that we could successfully reprogram differentiated cells using our destabilizing domain technology. However, the overall efficiency of this process was lower than reprogramming with unfused versions of the same proteins. Our studies suggest that fusing our destabilizing domain to the C-terminus of the Oct4 protein affects its ability to function properly and results in lower reprogramming efficiency.

© 2013 California Institute for Regenerative Medicine