In a study published Monday, researchers from the UC San Diego School of Medicine found a new marker to determine whether neurons — the main cells that make up our brain and spinal cord — will regenerate after an injury.
Neurons are among the slowest cells to regenerate after an injury, and many fail to regenerate entirely. According to the researchers, while scientists have made progress in understanding neuronal regeneration, it remains unknown why some neurons regenerate and others do not.
The study, published Monday in the journal Neuron, details how the authors used single-cell RNA sequencing, a method that determines which genes are activated in individual cells. The UCSD School of Medicine researchers tested their new biomarker discovery in mice, finding it was "consistently reliable in neurons across the nervous system and at different developmental stages."
"Single-cell sequencing technology is helping us look at the biology of neurons in much more detail than has ever been possible, and this study really demonstrates that capability," said senior author Binhai Zheng, professor in the Department of Neurosciences at the UCSD School of Medicine. "What we've discovered here could be just the beginning of a new generation of sophisticated biomarkers based on single-cell data."
According to the study, the researchers focused on neurons of the corticospinal tract, a critical part of the central nervous system that helps control movement. After injury, these neurons are among the least likely to regenerate axons — the long, thin structures that neurons use to communicate with one another.
"If you get an injury in your arm or your leg, those nerves can regenerate, and it's often possible to make a full functional recovery, but this isn't the case for the central nervous system," said first author Hugo Kim, a postdoctoral fellow in the Zheng lab. "It's extremely difficult to recover from most brain and spinal cord injuries because those cells have very limited regenerative capacity. Once they're gone, they're gone."
The researchers analyzed gene expression in neurons from mice with spinal cord injuries. They "encouraged these neurons to regenerate using established molecular techniques, but ultimately, this only worked for a portion of the cells," a UCSD statement reads.
By focusing on a relatively small number of cells — just over 300 — the researchers were able to look extremely closely at each individual cell.
"Just like how every person is different, every cell has its own unique biology," Zheng said. "Exploring minute differences between cells can tell us a lot about how those cells work."
To validate their findings, the researchers tested this molecular fingerprint — which they named the Regeneration Classifier — on 26 published single-cell RNA sequencing datasets. These datasets included neurons from various parts of the nervous system and at different developmental stages.
The team found that with few exceptions, the Regeneration Classifier "successfully predicted the regeneration potential of individual neurons and was able to reproduce known trends from previous research, such as a sharp decrease in neuronal regeneration just after birth," according to the study.
While the results in mice are promising, the researchers said that, currently, the Regeneration Classifier is a tool to help neuroscience researchers in the lab rather than a diagnostic test for patients in the clinic.
