A simple twist of cell fate

phys.org | 9/26/2019 | Staff
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How do a couple of universally expressed proteins in stem cells and developing embryos influence an individual cell's ultimate fate—whether it ultimately becomes, for example, a retinal cell, a heart muscle cell, or a stomach lining cell?

That's the question that Rajesh C. Rao, M.D., and his colleagues at the University of Michigan set out to answer.

Findings - Cell - Reports - Tools - Researchers

Their findings, published in Cell Reports, could lead to new tools for researchers studying different types of specialized cells—for which U-M was awarded provisional patents.

The research may also help illuminate an emerging class of anti-cancer drugs, WDR5 inhibitors—as the two proteins at the heart of the study, WDR5 and p53, have long been studied in relation to cancer, and the study sheds light on how WDR5 regulates p53, both directly and indirectly.

Scientists - Stem - Cell - Differentiation - Transcription

"Most scientists have worked to understand stem cell differentiation by looking at transcription factors and how they jump into the action at a very specific time and place," says Rao, an assistant professor of ophthalmology and pathology at Michigan Medicine, and the study's senior author.

"Our main interest is in epigenetics and how changes in chromatin—the packaging of DNA with proteins known as histones—affect the fate of stem cells," adds Rao, who is also the Leonard G. Miller Professor of Ophthalmology & Visual Sciences. "How does a ubiquitous transcription factor like p53 integrate time-sensitive inputs from WDR5, which is involved in chromatin modifications, to guide differentiation?"

Answer - Question - Interest - Scientists - Team

And while the detailed answer to that question is primarily of interest to other scientists, what the team observed in the lab is striking.

Using mouse embryonic stem cells—which the researchers work with because of their rapid propensity to differentiate into specific tissues within structures called "organoids"—the researchers found that by inducing a short delay in when WDR5 was expressed in precursor cells that emerge from embryonic stem cells, they could...
(Excerpt) Read more at: phys.org
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