The neuroscience "Rosetta Stone" is coming: the most complete map of brain cells to date

The Paper's reporter He Liping

The human brain is a complex thinking machine made up of tens of billions of neurons, and deciphering its mysteries is like reading a book in the sky. The first step in deciphering is to have a list of brain cell types. "Science" website reported on October 6 local time: a scientific research network of more than 400 researchers released the most complete map of brain cells to date.

The atlas also includes data on the molecules, functions, and physical states of neurons in mice, non-human primates, and human brains.

The above results come from the latest 17 papers in the international authoritative journal Nature. These studies collated the genetic characteristics of brain nerve cells and their morphology, location, and patterns of electrical activity. The researchers identified more than 100 cell types in addition to the human brain. The list could help researchers define cell types affected by brain diseases, identify corresponding cells in animal models, and better target those cells. Scientists believe that this map of brain nerve cells is comparable to the Rosetta Stone in neuroscience.

This is a very high evaluation, as the Rosetta Stone is a landmark artifact in human history and played a decisive role in deciphering Egyptian hieroglyphs. The stone tablet, which records the edict of the ancient Egyptian king Ptolemy V, was made in 196 BC. The stele was inscribed with the same contents in Greek, Ancient Egyptian and popular scripts of the time, giving archaeologists the opportunity to interpret the meaning and structure of Egyptian hieroglyphs that had been lost for more than a thousand years after comparing the contents of various language versions.

The study originated in the National Institutes of Health's (NIH) BRAIN Initiative Cell Census Network (BICCN). The project was launched in 2017 at a cost of approximately US$250 million. Many studies supported by BICCN have used genome sequencing to characterize brain nerve cell types. For example, a cellular RNA revealed a set of genes it recently transcribed to make proteins—its transcriptome. Other sequencing methods describe a cell's epigenome, a group of molecules distributed over its DNA that influence the expression of which genes.

Zhuang Xiaowei, a biophysicist at Harvard University and a biccnal researcher, believes that these are very powerful tools, but sequencing alone cannot tell the whole story. Researchers also need to know exactly where these nerve cells are in the brain, what their neighbors are, and how they interact.

BICCN collaborators agreed to focus first on one area: the primary motor cortex at the top of the brain, which coordinates muscle movements. They employ technology that captures multiple features at once. For example, a method developed by Zhuang's lab allows researchers to image hundreds or thousands of RNA sequences in brain tissue slices, revealing the cell's transcriptome and their relative position. Another method, Patch-seq, records the electrical activity of brain nerve cells, stains them to show their shape, and then sequences their RNA.

Mina Ryten, a clinical geneticist at University College London (UCL) who studies neurogenetic disorders, has far-reaching implications and could change the way researchers mimic brain diseases. BICCN data could help scientists determine which human brain cell types are most affected by specific mutations.

Editor-in-Charge: Li Yuequn