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“No” means “no” in stem cell fates, say Stanford researchers

gemma-evans-131781It's tough being a kid, when "No" seems to be the primary component in an adult's vocabulary. "Don't jump on the bed," "Don't touch the hot pan," and, my personal favorite as a parent, "No, you may not color your sister with permanent markers."

Being a young, developmentally impressionable cell is also no picnic. How to choose what developmental path to follow? Should it become a nerve cell, a skin cell, a muscle cell? Now stem cell researcher Marius Wernig, MD, along with postdoctoral scholar Moritz Mall, PhD, and former postdoctoral scholar Michael Kareta, PhD, have shown that young would-be neural cells also live in a culture of "no" in the form of a powerful repressor protein called Myt1l that actively blocks all other cell fates including skin, heart, lung and liver.

They published their results yesterday in Nature.

As I explained in our release:

The study marks the first identification of a near-global repressor that works to block many cell fates but one. It also suggests the possibility of a network of as-yet-unidentified master regulators specific to each cell type in the body.

Myt1l works in conjunction with another protein that channels the developing cell into the neural cell fate by encouraging the expression of nerve-specific genes. Wernig explained:

Together, these proteins work as a perfect team to funnel a developing cell, or a cell that is being reprogrammed, into the desired cell fate... It’s a beautiful scenario that both blocks the fibroblast program and promotes the neuronal program. My gut feeling would be that there are many more master repressors like Myt1l to be found for specific cell types, each of which would block all but one cell fate.

Blocking Myt1l expression even in adult neural cells can cause them to lose their way, the researchers found. They begin to express non-neuronal genes and become less efficient at transmitting nerve signals. Because Myt1l has been found to be mutated in some cases of autism, schizophrenia and major depression, the research may one day offer new therapeutic avenues for affected people.

Wernig is a member of Stanford's Institute for Stem Cell Biology and Regenerative Medicine.

Previously: Bridging the stem-cell gap: Stanford researchers identify unique transition state"It's not just science fiction anymore": Childx speakers talk stem cell and gene therapy and Congratulations to Marius Wernig, named Outstanding Young Investigator by stem cell society
Image by Gemma Evans

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