http://medicalxpress.com/news/2011-10-scientists-liver-cells-neurons-technique.html
Fully mature liver cells from laboratory mice have been transformed directly into functional neurons by researchers at the Stanford University School of Medicine. The switch was accomplished with the introduction of just three genes and did not require the cells to first enter a pluripotent state. It is the first time that cells have been shown to leapfrog from one fundamentally different tissue type to another.
The accomplishment extends previous research by the same group, which showed in 2009 that it is possible to directly transform mouse fibroblasts, or skin cells, into neurons.
“These liver cells unambiguously cross tissue-type boundaries to become fully functional neural cells,” said Marius Wernig, MD, PhD assistant professor of pathology and a member of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine. “Even more surprising, these cells also simultaneously silence their liver-gene expression profile. They are not hybrids; they are completely switching their identities.”
The cells make the change without first becoming a pluripotent type of stem cell — a step long thought to be required for cells to acquire new identities.
Wernig is the senior author of the research, published online Sept. 29 in Cell Stem Cell. Postdoctoral scholar Samuele Marro, PhD, is the first author of the study.
The researchers used a technique developed by Stanford bioengineer Stephen Quake, PhD, to analyze the gene expression profiles of individual hepatocytes (liver cells) and fibroblasts to show that both types of transformed cells not only begin looking and acting like true neurons, they also decisively shut down nearly all gene expression associated with their former, very different identities.
“This is fascinating,” said Wernig. “We can imagine ways that the three introduced factors could stimulate neural gene expression, but how do they also down-regulate two completely unrelated donor networks — those of skin and liver cells?”
Understanding how this down-regulation works will help scientists and clinicians determine whether these so-called transdifferentiated cells can be used to learn more about diseases or even be safely used in human therapy. It would not be good, for example, if newly derived neurons began to again express skin or liver proteins. It also may help researchers understand the process of development, during which cells commit to certain fates while also turning off other potential pathways.
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