Previous methods for creating embryonic stem cell-like cells have relied on the introduction of DNA that encodes four transcription factors, proteins that play a role in the production of genes. The limitation of this method is that three of the four genes that code for these transcription factors -- oct4, klf4 and c-myc are oncogenes, meaning they promote the uncontrolled cell growth characteristic of cancer.
In the current study, led by Robert Judson, a graduate student in the Blelloch lab, the scientists induced pluripotency using a combination of infection and transfection. The infection involved introducing three viruses, each containing a transcription factor known to induce pluripotency. The transcription factor for c-myc was not included. The transfection involved a simple process in which the tiny microRNA molecules were mixed with a lipid, allowing them to pass through the cell membrane. By labeling the fibroblast cells, they showed that the treated cells could be incorporated into a mouse embryo and become every cell type in the adult animal -- including germline cells that would produce the next generation of mice.
"These are transient, non-coding molecules that do not incorporate into the genome, but promote self-replication and have the potential to induce pluripotency," Blelloch says. "They do their thing -- turn a somatic cell into an embryonic stem cell-like one -- and then they're gone."
"MicroRNAs give us a new tool to manipulate the fate of cells," Blelloch says.
MicroRNAs are snippets of single-stranded RNA that prevent a gene's code from being translated from messenger RNA into protein. They were debuted in 1993, when scientists reported the discovery of a microRNA in the microscopic roundworm C. elegans. Since then, the field has "exploded," says Blelloch, with hundreds of microRNAs discovered in the last eight years across a broad rang
|Contact: Jennifer OBrien|
University of California - San Francisco