by Jane Qiu
Mouse, human and monkey cells can be induced to pluripotency
In 2006, stem cell scientists were shocked by the discovery that differentiated mouse cells can be reprogrammed to behave like embryonic stem cells. All it took was the addition of a few pluripotency genes. The following year, reports came that human cells can also be reprogrammed. This year, a third species has joined the ranks. A study published in Cell Stem Cell shows that a similar approach used for mouse and human cells can generate induced pluripotent stem cells from adult skin fibroblasts of the rhesus macaque.
A team led by Hongkui Deng at Peking University in Beijing, China, and colleagues, was able to generate 10 induced pluripotent stem (iPS) cell colonies for every 30,000 monkey skin cells that were infected with retroviruses containing genes for the transcription factors OCT4, SOX2, KLF4 and c-Myc — the genes that Shinya Yamanaka of Kyoto University, Japan, had shown were able to reprogram mouse and human cells.
The iPS cells expressed markers of embryonic stem (ES) cells that were not expressed in the fibroblast population. The gene-expression profile of monkey iPS cells was more similar to that of ES cells than to that of fibroblasts. In contrast to the genes in adult cells, which had high levels of methyl groups known to silence gene expression, most genes in the iPS and ES cells were free of methyl groups.
Cultured iPS cells also exhibited similar behaviours to ES cells. They were able to form bell-shaped embryoid bodies and then differentiate into cell types containing the three germ layers as judged by morphologies and gene expression. They could then be induced to directly differentiate into cell lineages of the three germ layers. In addition, the iPS cells that were injected into mice lacking immune responses developed into tumours containing a variety of cell types — a standard test for demonstrating the pluripotency of stem cells.
As the rhesus macaque is the most relevant primate model for many human diseases, highly efficient generation of monkey iPS cells will allow researchers to investigate treatments for various diseases in this model, says Deng. Comparisons between monkey and human cells might help researchers predict how results in live monkeys could translate to humans.
"This is an interesting study and shows that the mechanism [of reprogramming somatic cells by the four transcription factors] may be conserved in most organisms," says Shoukhrat Mitalipov of the Oregon Health & Science University at Beaverton, Oregon. However, he cautions that the transcription factors, especially the oncogenes KLF4 and c-Myc, might cause cancer in recipient organisms; with the iPS cells in hand, however, this possibility can be explored in monkeys.
Source: Nature