Tumour suppressor p53 also controls somatic cell reprogramming

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London, August 10 (ANI): A new study has revealed that the tumour suppressor p53 not only stops cells that could become cancerous in their tracks, but it also controls somatic cell reprogramming.

Scientists have made significant advances in learning how to reprogram adult human cells such as skin cells into so-called induced pluripotent stem cells (iPSCs), but still the reprogramming efficiency is still woefully low.

The new study, led by researchers at the Salk Institute for Biological Studies, gives new insight why only a few cells out of many can be persuaded to turn back the clock.

"Although we have been able to reprogram specialized cells for a while now, there had been nothing known about the control mechanisms that prevent it from happening spontaneously in the body and why it has been so hard to change their fate in a Petri dish," Nature magazine quoted Dr. Juan-Carlos Izpisúa Belmonte, a professors in the Gene Expression Laboratory, who worked closely with Dr. Geoffrey M. Wahl, also a professor in the Gene Expression Laboratory, as saying.

The researchers say that their findings bring iPSCs technology a step closer to fulfilling its promise as source of patient-specific stem cells but also force scientists to rethink the development of cancer.

"There's been a decade-old idea that cancer arises through the de-differentiation of fully committed and specialized cells but eventually it was discarded in favor of the currently fashionable cancer stem cell theory. Now, that we know that p53 prevents de-differentiation, I believe it is time to reconsider the possibility that reprogramming plays a role in the development of cancer since virtually all cancer cells lose p53 function in one way or another," says Wahl.

Taking about some fresh ideas that the new study has provided the scientists with to test in the lab, Wahl said: "Normally, cells don't reprogram so there must be a mechanism in place that prevents it. We knew that c-Myc and some of the other genes that are required for reprogramming activate the tumour suppressor p53 and we wondered whether it had any part in it."

During the study, the researchers observed that in cells genetically engineered to lack p53, reprogramming efficiency was at least 10-fold increased compared to control cells, demonstrating that p53 clearly played an important role in reigning in cells trying to revert back into a stem-like state.

Because iPSCs generated with the full complement of reprogramming factors run the risk to turn malignant, Belmonte and his team wanted to know whether mouse cells lacking p53 could be reprogrammed using only two factors, Oct4 and Sox2.

The cells readily converted into iPSCs and gave rise to healthy, full term mice that were able to reproduce passing the ultimate test for pluripotent embryonic stem cells.

"This very successful collaboration is a prime example of what makes the Salk such a special place. Juan Carlos and I talk every day and we approach the same question from very different perspectives. He comes from a developmental biology perspective, while I come from the cancer side but when put together they can make for a great story," says Wahl.

A research article describing the study has been published in the advanced online edition of the journal Nature. (ANI)

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