Study Identifies Previously Unknown Role for Oligodendrocyte Precursor Cells

Researchers in Seattle have captured images of oligodendrocyte precursor cells (OPC) engaging in synaptic pruning—a previously unknown role for cells that are relatively understudied considering they make up 5% of all central nervous system cells.  

As neurons form new connections and lose old ones, other cells in the brain clean up and dispose of the physical machinery from the unwanted connections via phagocytosis, or cell eating. However, this synaptic clearing was thought to be the purview of microglia, a kind of immune cell known informally likened to the brain’s garbage disposal system.

That OPCs also perform this task was a complete surprise, according to JoAnn Buchanan, Ph.D., a scientist at the Allen Institute, who stumbled upon OPCs nibbling on nearby neurons while scanning the mouse brain cells on her computer screen. “[It] was believed to be the main purpose of microglia — they’re known as the main phagocytes of the brain,” Buchanan said. “And all of a sudden, here’s this other cell doing it.”

OPCs are known to give rise to another kind of brain cell known as oligodendrocytes, which form thick, white insulation around bundles of nerves. That electrical insulation, also called myelin, makes up the brain’s white matter and is also the key brain structure to succumb to damage in the autoimmune disease multiple sclerosis. But scientists have suspected for awhile that OPCs do something else besides generate these insulating brain cells, because there are so many of them in the brain.

“These cells are becoming more appreciated now,” said Dwight Bergles, Ph.D., a professor of neuroscience at Johns Hopkins University School of Medicine and a co-author on the OPC study. “But you would be hard-pressed to find them discussed in neuroscience textbooks, and that’s despite the fact that they make up about 5% of all cells in the central nervous system.”

The discovery came about thanks to a massive dataset Buchanan helped create. The collection of detailed 3D shapes is comprised of nearly 200,000 brain cells present in a grain-of-sand-sized piece of a mouse brain. The dataset, which is publicly available,  was generated using an electron microscope, which captures images by bombarding a slice of brain with a beam of focused electrons. Because electrons have a much shorter wavelength than light, electron microscopes can capture tiny details at much higher resolution than light microscopes can. The kind of electron microscopes used at the Allen Institute pass a beam of electrons through a thin slice of material; the grain of sand sized piece of mouse brain was sliced into 25,000 incredibly thin slices before the team of researchers imaged it.

Buchanan says the dataset is large enough to capture complex, branching neurons and other brain cells in their entirety and in relationship with neighboring cells. But most importantly for the discoveries Buchanan made about OPCs, the dataset has been computationally stitched together from its original super-thin slices into 3D visualizations of entire cells.

The findings were published recently in Proceedings of the National Academy of Sciences.