A discovery by UCSB stem cell researchers may prove critical in the fight against cancer.
Published in the May 1 issue of the journal Cell, the study detailed how UCSB scientists located a control protein that can cause stem cells to differentiate into any of the numerous cell types that form the human body – an ability known as pluripotency.
Their research explains how the cells function and how they either renew or morph into other components of the human body. Since tumor stem cells play a central role in the evolution of tumors, the study is particularly crucial for understanding the spread of cancer.
According to Kenneth Kosik, a professor of biology at UCSB and senior author of the study, his team’s findings build on a breakthrough from a-year-and-a-half ago. In the former study, two independent research teams – one led by UCSB adjunct professor James Thomson – were able to convert differentiated cells back to stem cells using a series of transcription factors.
“You can take a cell, a skin cell, or possibly any cell of the body, and revert it back to a stem cell,” Kosik said in a press release. “You take the transcription factors that are required for the pluripotent state, and you get them to express themselves in the skin cells; that’s how you can restore the embryonic stem cell state. You clone a gene … shoot them into a stem cell. [When those genes] get turned on … it goes back to the embryonic pluripotent stem cell state.”
Through the study, scientists discovered the control mechanism – a microRNA called miR-145 – that slows down transcription factors, causing a cell to differentiate into kidney, liver or other cells. However, a second factor known as OCT4 inhibits miR-145, allowing the cellular transformation to work both ways.
With this discovery, Kosik said, his team has pinpointed a cellular mechanism intrinsic to the body.
“We now have discovered that the control feedback inhibits the stem cell state, once [the cell] says ‘now I want to become a kidney cell,’ you don’t want the cell to go the other direction, [the cell] needs to be committed to that,” Kosik said.
According to Kosik, the knowledge of how stem cells convert into other cells can be useful in the fight against cancer, since tumors possess their own stem cells which fuel their growth.
“What happens is that there are cells in the tumor which are tumor stem cells,” Kosik said. “They have the potential to become other cells in the tumor, its a similar process…[Forcing the cells] from a stem cell state to a differentiated state with the same RNA may limit the growth of the tumor.”
Na Xu, a postdoctoral fellow at UCSB, was the major contributor to the study according to Kosik.
“Na Xu deserves enormous credit for this work,” Kosik said in a press release. “She performed nearly every experiment in the paper and was the major contributor to the ideas in the paper.”
While the recent findings of the study will not erase the importance of embryonic stem cells in regenerative medical research, Kosik said the ability to convert individual’s own cells into useful stem cells may redirect emphasis on embryonic cells.
[The finding] doesn’t remove the need, but may reduce the need for embryonic stem cells,” Kosik said. “Reprogramming may let us get around the need for embryonic stem cells.”