Researchers have discovered that children's brains can contain cells with their mother's DNA and that these cells can persist for decades.

The findings, which were posted to the preprint database bioRxiv June 10 but have not been peer-reviewed yet, are part of a growing body of work showing that a mother and fetus exchange cells during pregnancy ‪—‬ a phenomenon known as "microchimerism." Previously, scientists had found that a mother's brain harbors cells with her children's DNA.

The findings are important for several reasons, said Amy Boddy, co-director of the Microchimerism, Human Health and Evolution Project at the University of California, Santa Barbara, who was not involved in the study. Past work mostly found evidence of maternal microchimerism in infancy, and in blood samples, she told Live Science in an email. "What's exciting here is that it's tissue, not blood; it's real human data, not an animal model; and the methods are cutting-edge."

More broadly, the work reinforces the idea that microchimerism is "a normal process of mammalian biology," Boddy said.

Hunting down maternal cells in the brain

Before this study, there was sparse evidence for maternal microchimeric cells in brains, mostly because it is hard for researchers to get samples of human brain tissue and DNA from both parents and their children.

To overcome this challenge, a team led by Sami Kanaan, a staff scientist at the Fred Hutchinson Cancer Center in Seattle, analyzed brain tissue that had been surgically removed from dozens of children with severe epilepsy as part of their treatment. The patients ranged in age from 28 days to 19 years at the time of their surgery, and their mothers provided DNA samples through cheek swabs.

Kanaan's team used a tool called quantitative PCR to identify and count maternal cells hiding among millions of cells in the children's brains.

Out of 37 mother-child pairs, 26 children ‪—‬ 70% ‪—‬ had their mother's cells in their brains. These maternal cells were distributed across multiple regions of the brain, including the frontal, temporal and parietal lobes, which sit on the brain's outer surface, and the hippocampus, which is buried deep inside. Each sample had, on average, about 2.2 maternal cells per 100,000, though one sample from the hippocampus had 459 maternal cells per 100,000 and 11 children had no evidence of maternal DNA in their brains.

That prevalence is probably underestimated, Boddy said, "due to the limits of detecting rare cells at low frequency with this method."

Being a firstborn child seemed to increase the odds of having maternal cells in the brain. Of the children who carried their mother's cells, 14 were firstborns and 12 were later-born. In contrast, among the children who didn't have these cells, only one was a firstborn and 10 were later-born.

Using a technique called single nucleus RNA sequencing, which reveals what a cell is doing by showing which genes within the cells are switched on, the researchers found that the maternal cells had transformed into several types of brain cells. Likely, these cells were originally leukocytes and stem cells and had been transferred to the fetus via the placenta or during pregnancy or breastfeeding.

The transformed cells included neurons; oligodendrocytes, which produce the protective sheath around neurons; astrocytes, which support many brain functions and help fuel neurons; microglia, the brain's immune cells; and endothelial cells, which line blood vessels.

"Being able to use single-nucleus RNA sequencing to identify what type of cells the maternal microchimeric cells actually are is amazing," Boddy said. "We've been so limited in understanding the function of these cells, and papers like this, with these methods, are getting us closer."

Checking healthy brains

To see whether these findings also applied to people without epilepsy, the researchers examined brain autopsy data from 29 individuals with no known neurodevelopmental conditions, ranging in age from 22 weeks of gestation to 40 years. They also analyzed brain tissue from three men in their late 80s and early 90s without any known brain conditions originally collected as part of an Alzheimer's disease study.

In total, the researchers found foreign cells in 25 of 32 people — about 78% — including in the brain of a man in his 90s.

The researchers suspect these foreign cells are maternal, but they couldn't confirm it because they didn't have DNA from the mothers. It is possible that the foreign cells came from a twin; an older sibling; a past pregnancy, miscarriage or abortion (in females); or, rarely, from a maternal grandmother, the team wrote in their paper.

As in the epilepsy patients, these cells had matured into several types of working brain cells. In younger brains, they most often became a specific kind of neuron, a layer 2/3 neuron, while in older brains, maternal cells were more likely to be microglia.

Given that these microchimeric cells take on very different roles, it would be interesting to know whether that diversity reflects their origins ‪—‬ for example, whether they came from a mother, an older biological sibling or a maternal grandmother, said Dr. Sing Sing Way, a microchimerism researcher at Cincinnati Children's Hospital Medical Center who was not involved in the study.

The number of maternal cells declined with age, but they never completely disappeared.

Boddy said the findings mostly raise new questions. "Do we maybe need microchimeric cells to 'help out'?" she asked. "Is diversity of cells in the brain important, or is it just a byproduct of being a placental mammal?”

Because microchimeric cells appear to be common, Boddy suspects they "are doing an important job in the brain, so understanding their function could be very important for understanding healthy brain development."

By using new analytical tools to pinpoint microchimeric cells, the study "pushes the boundaries" of previous research, but future studies would benefit from larger and more uniform datasets, Way said. That would mean obtaining more brain biopsies, analyzing more cells from each sample, collecting specimens at different ages, and sampling similar brain regions across individuals to better compare the results.

This article is for informational purposes only and is not meant to offer medical advice.

Scientists long thought that when RNA kick-started life on Earth 4 billion years ago, it could form only small, simple structures. But new research shows that naturally occurring RNA molecules can also adopt large, sophisticated geometries, like filaments and cages. Now, scientists wonder whether the structures were present at life's beginning.

According to an idea known as the RNA world hypothesis, RNA-based life-forms preceded modern ones that use DNA and protein. RNA, a molecular cousin of DNA, still plays roles in modern cells but does not serve as the primary genetic material. By comparison, primordial species used RNA to store genetic information and to catalyze reactions as stand-in enzymes.

Proteins eventually dominated as enzymes, perhaps because they can fold into more diverse figures than RNA can. That's because proteins are composed of 20 types of subunits, called amino acids, each with a unique structure, whereas RNA is composed of only four subunits, called nucleotides, that all adopt similar shapes.

Scientists originally thought that only proteins were varied enough to assemble into large structures, but a new paper has demonstrated that RNA — though more limited in its variety — also has the capacity to form these large configurations. The research was posted to the preprint server bioRxiv July 1 and has not been peer-reviewed yet.

"We show RNA can do things which we have never seen before," said study co-author Lin Huang, an RNA biologist at Sun Yat-Sen University in China. "It suggests that at the origin of life RNA could assemble into all kinds of shapes," he told Live Science.

Huang and his colleagues had hypothesized that RNA molecules could link together if they possessed sequences that fold into "kissing stem loops." This occurs when an RNA strand folds over on itself, forming a structure that resembles a loop in a shoelace. If loops from different RNAs bond together, or "kiss," the molecules could link up and form larger complexes, the researchers proposed.

After sifting through a bevy of RNA sequences, the researchers found a family of RNA molecules encoded by bacteriophages ‪—‬ viruses that infect bacteria ‪—‬ that form these loops. They purified several of these RNA molecules in the lab, allowed them to assemble in a dish, and then captured their structures using cryo-electron microscopy.

They discovered that some of the RNA molecules formed long filaments. These resembled protein-based filaments such as the cellular cytoskeleton, a scaffold that participates in many functions, including shaping and moving the cell.

Other RNA molecules assembled into cages as large as common viruses. Some of these took the form of an icosahedron — a 3D shape that is built from 20 equilateral triangles and resembles a soccer ball. Many viruses, including herpesviruses, package their genome into protein-based icosahedra called capsids. This raises a question: Could RNA-based capsids have packaged genomes in the RNA world?

This work demonstrates that RNA had the capacity to assemble into these elaborate structures during the RNA world, Huang said, but that doesn't prove it actually happened.

"I definitely think that environmental parameters are a question," Anna Medvegy, an evolutionary biologist at Eötvös Loránd University in Hungary, told Live Science in an email. "Can these structures form in the environment in which the hypothetical RNA World existed?" said Medvegy, who was not involved in the new work.

If scientists could recreate these environmental conditions at the dawn of life, such as high temperatures and low pH, and still observe that these structures take shape, that would strengthen the theory that they could have been present in the RNA world, she said.

Although the RNA cages and filaments were large, Huang's team generated them using only short RNA strands, each no longer than 200 subunits. Medvegy said long RNAs are susceptible to breaking, so if short strands can assemble into these structures, that provides more promise that these multi-tiered molecules could have formed in the RNA world.

Another question is whether these elaborate RNA complexes currently assemble inside the bacteriophage-infected bacteria from which they were derived. So far, Huang's team has only seen these structures form in a lab dish, so they need to determine if factors inside bacteria, such as proteins, would either disrupt or enable their formation inside cells.

Beyond providing insight into life's beginnings, these RNA cages could have potential applications in biotechnology, Huang thinks. Efforts are underway to use DNA folded into "DNA origami" to deliver drugs into cells, and Huang thinks DNA's older cousin, RNA, could one day play a similar role in medicine.