Reprogramming of human somatic cells back to pluripotent embryonic stem cells

Reprogramming of human somatic cells back to pluripotent embryonic stem cells

Funding Type: 
New Faculty I
Grant Number: 
RN1-00536-B
Award Value: 
$1,414,664
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

During the reporting period, we have made significant progress toward the following research aims: (1) Using the reprogramming assay system established in year one, we continue to screen and identify small molecules that can replace reprogramming transcription factors to generate induced pluripotent stem (iPS) cells from human somatic cells. Based on our earlier success on reprogramming neonatal human keratinocytes and endothelial cells into iPS cells using a single transcription factor, Oct4, and a combination of small molecules, we further optimize the conditions that allowed us to reprogram clinically more relevant and practical adult human keratinocytes and also mesenchyml/fibroblastic cells (isolated from amnion fluid) into full iPS cells. (2) Using standard assays, we have characterized those iPS cells to be pluripotent in vitro and in vivo. (3) Most importantly, we characterized a new fundamental mechanism of reprogramming involving a metabolic switch. Such new mechanistic insight has since provided new guidance and strategies to optimize the reprogramming conditions.

Year 2

During the reporting period, we have made significant progress toward discovering new molecules that can enhance reprogramming of human somatic cells to become pluripotent stem cells with minimal genetic manipulation. Specifically, using the reprogramming assay system established, we continued to screen and identify new small molecules that can enhance reprogramming efficiency under a single reprogramming factor/Oct4 condition to generate induced pluripotent stem (iPS) cells from human somatic cells. Using standard assays, we have characterized those iPS cells to be pluripotent in vitro and in vivo. Most importantly, we characterized another new fundamental mechanism of reprogramming involving mitochondrial metabolism. Such new mechanistic insight has since provided new guidance and strategies to optimize the reprogramming conditions.

Year 3

During the reporting period, we have made significant progress toward the following research aims: (1) Using the reprogramming assay system established, we continued to screen and identify new small molecules that can enhance reprogramming efficiency under a single reprogramming factor/Oct4 condition to generate induced pluripotent stem (iPS) cells from human somatic cells. (2) Using standard assays, we have characterized those iPS cells to be pluripotent in vitro and in vivo. (3) Most importantly, we characterized new fundamental mechanism of reprogramming involving metabolism and epigenetics. Such new mechanistic insight has since provided new guidance and strategies to optimize the reprogramming conditions.

© 2013 California Institute for Regenerative Medicine