"These cells are not as far along on the differentiation pathway, so they're easier to back up to an earlier state," said first author and postdoctoral scholar Ning Sun, PhD, who conducted the research in both Longaker's and Wu's laboratories. "They are more embryonic-like than fibroblasts, which take more effort to reprogram."
These reprogrammed iPS cells are usually created by expressing four genes, called Yamanaka factors, normally unexpressed (or expressed at very low levels) in adult cells.
Sun found that the fat stem cells actually express higher starting levels of two of the four reprogramming genes than do adult skin cellssuggesting that these cells are already primed for change. When he added all four genes, about 0.01 percent of the skin-cell fibroblasts eventually became iPS cells but about 0.2 percent of the fat stem cells did soa 20-fold improvement in efficiency.
The new iPS cells passed the standard tests for pluripotency: They formed tumors called teratomas when injected into immunocompromised mice, and they could differentiate into cells from the three main tissue types in the body, including neurons, muscle and gut epithelium. The researchers are now investigating whether the gene expression profiles of the fat stem cells could be used to identify a subpopulation that could be reprogrammed even more efficiently.
"The idea of reprogramming a cell from your body to become anything your body needs is very exciting," said Longaker, who emphasized that the work involved not just a collaboration between his lab and Wu's, but also between the two Stanford institute
|Contact: Krista Conger|
Stanford University Medical Center