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The brain remains one of the great mysteries of science – its function, pathology and even fundamental structure are frontiers modern science is still attempting to fully understand.

A potentially huge discovery of a whole subtype of brain cells that had been heretofore unknown is reported this week in Science.

The methylation processes of the cells at the molecular level were the signature that showed the different types of cells, report the scientists from the Salk Institute and the University of California, San Diego.

Instead of identifying the brain cells based on RNA molecules – which can change when exposed to different conditions or even just over the course of the cycles of a day – they looked at the methylation of the cells to identify the differences in the chemical processes of brain cells.

“This study opens a new window into the incredible diversity of brain cells,” said Eran Mukamel, a senior author of the study, from UC, San Diego.

The scientists isolated neurons from the brains of mice, and a deceased 25-year-old man. The frontal cortexes yielded more than 3,300 neurons from the rodents, and more than 2,700 from the human.

They sequenced the methylomes of each one of those cells, using a process they developed called snmC-seq, which assesses two methylation types, that of the DNA sequences involving cytosine and guanine, and those that don’t use those sequences.

They found the mice had 16 neuronal cluster types at the single-nucleus level, while the human showed 21 varieties. Together, the diversity indicates there is more complexity than had been suspected, especially in the deep brain layers of the cortex.

“Our research shows that we can clearly define neuronal types based on their methylomes,” said Margarita Behrens, a senior author on the paper, from Salk. “This opens up the possibility of understanding what makes two neurons – that sit in the same brain region and otherwise look similar – behave differently.”

The work could continue to include a mapping of a whole new dimension of the brain, they added.

“There are hundreds, if not thousands, of types of brain cells that have different function and behaviors and it’s important to know what all these types are to understand how the brain works,” said Chongyuan Luo, a Salk scientist and one of the first authors. “Our goal is to create a parts list of both mouse and human brains.”

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