Whitehead Institute researchers have developed a novel method of removing potential cancer-causing genes during the reprogramming of skin cells from Parkinson’s disease patients into an embryonic-stem-cell-like state. Scientists were then able to use the resulting induced pluripotent stem (iPS) cells to derive dopamine-producing neurons, the cell type that degenerates in Parkinson’s disease patients.
The work marks the first time researchers have generated human iPS cells that have maintained their embryonic stem-cell-like properties after the removal of reprogramming genes. The findings are published in the March 6 edition of the journal Cell.
Removing the reprogramming genes is also important because of those genes’ effect on an iPS cell‘s gene expression (a measure of which genes the cell is using and how much it’s using those genes). When the researchers compared the gene expressions of human embryonic stem cells to iPS cells with and without the reprogramming factors, iPS cells without the reprogramming genes had a gene expression closer to human embryonic stem cells than to the same iPS cells that still contained the reprogramming genes.
“The reprogramming factors are known to bind to and affect the expression of 3,000 genes in the entire genome, so having artificial expression of those genes will change the cell’s overall gene expression,” Dirk Hockemeyer, who is also a co-author of the Cell article. “That’s why the four reprogramming genes can mess up the system so much. From now on, it will be tough for researchers to leave the reprogramming genes in iPS cells.”