Brain’s adult stem cells born early

Understanding their origin boosts chance of exploiting damage-repair candidates

birth of neural stem cells

EARLY ON  In mice, many cells that go on to become adult neural stem cells (yellow) are born around embryonic day 14.5 (middle panel). Fewer are born on embryonic day 12.5 (left panel) and day 18.5 (right panel).

L.C. Fuentealba et al/Cell 2015

Stem cells in the adult brain are born early in embryonic life, scientists report in the June 18 Cell. Understanding when and how these cells arise is a step toward designer cells that could be used to repopulate damaged brain areas. 

Neural stem cells hold great promise for repairing brains because they are capable of continually producing new nerve cells, even in an adult brain. “We know that that they are there, but the question is, ‘How did they get there?’” says neuroscientist Chris Fasano of the Neural Stem Cell Institute in Rensselaer, N.Y. “This paper, for the first time, reports that journey.”

Researchers led by Arturo Alvarez-Buylla of the University of California, San Francisco identified neural stem cells’ birthdays in mouse brains with a compound called BrdU, which works its way into newly created cells. Most of these adult neural stem cells are born early in embryonic life — between embryonic day 13.5 and 15.5 and hang around into adulthood, the team found. “The embryonic brain is planning for the future,” by setting aside this population of cells, Alvarez-Buylla says.

Once these cells are created, they don’t seem to be actively dividing very much throughout a mouse’s life, the team found. “They sit for long times,” says study coauthor Luis Fuentealba, now at Neurona Therapeutics in San Francisco. The results suggest that these cells kick into gear and create new nerve cells only when needed, he says.

The researchers also labeled these cells with unique “bar codes,” stretches of DNA letters that weave into the cells’ genetic material and get passed down to daughter cells. Like reunion T-shirts, these bar codes identify members of the same family. Early in development, adult neural stem cells shared parents with nerve cells in the cortex, the striatum and the septum, the researchers found.

That shared heritage “makes common sense,” Fasano says, since all cells in the body ultimately come from when a sperm meets an egg. The new study reveals some of the details of this common early ancestry.

The embryonic development of mice and people are thought to be similar, Fuentealba says, suggesting that these neural stem cells may be set aside early on in people, too.

Now that scientists better understand when these cells are born, the next question is how, Fuentealba says. If scientists can figure out the particular signals that coax embryonic cells to produce certain kinds of brain cells, including these adult stem cells, then they could raise specially designed nerve cells to help repair the brain in certain cases. Specialized nerve cells could help replenish the depleted brain areas that cause Parkinson’s disease, for instance. 

Laura Sanders is the neuroscience writer. She holds a Ph.D. in molecular biology from the University of Southern California.

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