Two marmosets looking in different directions.

Naturally chimeric marmosets present opportunities for autism research | Spectrum | Autism Research News

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Sibling Rivalry: Marmosets share some microglia with their birthmates, a trait that may make them well suited to studies of autism-related variants.

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Newly discovered aspects of cells in the marmoset brain may make the animals even more useful for autism research than they already are, according to two unpublished studies presented yesterday at Neuroscience 2022 in San Diego, California. These little monkeys, which mimic human social behavior more closely than rodents, have become a popular model for studying genetic conditions linked to autism.

One of the studies shows that marmosets are naturally chimeric: the animals carry cells from another animal, in this case, immune cells called microglia from their biological siblings. Because this chimerism arises naturally during prenatal development, marmosets do not reject foreign cells.

“We try to make chimeric models in mice all the time, but we get it for free in marmosets,” says study researcher Ricardo del Rosario, a computational biologist at the Broad Institute in Cambridge, Massachusetts, who presented the findings.

Born as twins or triplets, marmosets share blood circulation and exchange blood stem cells in the womb. Some of these cells end up differentiating into microglia that eventually form a permanent home in the brain of others.

Microglia and other cells in the brains of autistic people tend to have dysregulated gene expression, according to research published earlier this month. And microglia are thought to play a crucial role in pruning synapses during early brain development, supporting typical connectivity between neurons.

Much of a marmoset’s microglia carry that animal’s own genetic signature, but 20 percent to 52 percent may come from a sibling, RNA sequencing in 137 brain tissue samples from 11 different marmosets showed.

This feature could make the marmoset a strong model for investigating the effects of autism-related genetic mutations on microglia, says del Rosario.

Researchers could use these chimeras to see how a genetic variant present in a marmoset affects the gene expression and behavior of its microglia compared to those of its wild-type siblings. “You have this side-by-side comparison,” she says.

Measuring two genotypes in the same model animal would be useful, but could also present a challenge, says Fenna Krienen, an assistant professor of neuroscience at Princeton University, who is not involved in del Rosario’s study but has also studied marmoset brains as part of the same team at the Broad Institute. Examining the genetics of these animals would likely require single-cell sequencing to avoid merging microglia that come from different siblings.

AAutism research will also benefit from another marmoset trait: The animal’s brain cells develop in lineages that are much more similar to those seen in people than in mice, according to an unpublished study Krienen presented yesterday.

Marmoset brain cells tend to retain the genetic signature of the region where they originally developed, even if they end up migrating to another area, single-nucleus RNA sequencing of cells from 16 brain areas showed. This recaps what you see in people, says Krienen.

And it suggests that the brain of a marmoset models this aspect of neurodevelopment better than the brain of a mouse. “There is a major grade shift in molecular similarity” in marmoset brains compared to mouse brains, she says. Krienen and her colleagues published the findings in bioRxiv in October.

Read more reports of Neuroscience 2022.

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