This is the first complete cellular map of adult mouse brain showing neural neighborhoods for more than 5,300 cell types

After six years of intensive research and the analysis of 32 million cells, a team of scientists has completed the first comprehensive cellular blueprint of a mammal’s brain.

Today, in a series of 10 articles published in NaturThe Value of Spatial Context in Brain Mappinge, a collaborative network of researchers introduced a detailed brain atlas.

This atlas details every cell in the adult mouse brain, categorizing them by type and location. Utilizing cutting-edge cell profiling technologies, the team discovered over 5,300 distinct cell types, a significantly higher number than previously recognized, and meticulously mapped their distribution across the brain’s complex structure.

According to Hongkui Zeng, Ph.D., Executive Vice President and Director at the Allen Institute for Brain Science, having this exhaustive “inventory” of brain components is a major step forward in understanding brain functionality.

Zeng, who spearheaded one of the pivotal studies, says, “This is a landmark achievement that really opens the door for the next stage of investigations of the brain’s function, development and evolution, akin to the reference genomes for studying gene function and genomic evolution.

“My colleagues said that the 5,000 cell types we identified will keep neuroscientists busy for the next 20 years trying to figure out what these cell types do and how they change in disease.”

This collective effort marks a significant milestone for the BRAIN Initiative Cell Census Network (BICCN), supported by the National Institutes of Health (NIH). The project involved the contributions of hundreds of researchers and was part of the NIH’s Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative.

“We’re seeing the building blocks of the brain’s circuits”

Through a synergistic blend of single-cell RNA sequencing and spatial transcriptomics, Zeng and her team have illuminated the profound complexity and diversity of the brain. These methodologies enabled them to map gene expression in individual cells and pinpoint their exact locations in the brain.

One of the key insights from the atlas is the strong link between a cell’s genetic identity and its spatial placement. Zeng highlights this as crucial, indicating that a cell’s location significantly influences its function and offers a window into the evolutionary journey and complex interplay of various brain regions.

“We’re seeing the building blocks of the brain’s circuits,” Zeng explains. “the brain’s organization likely reflects its evolutionary history.”

A notable observation from the study is the distinct cellular structure of the brain’s lower (ventral) and upper (dorsal) segments. The ventral region, being more ancient, displays a rich tapestry of interconnected cells, whereas the newer dorsal region is characterized by fewer, yet more diverse, cell types.

This distinction might hold the key to understanding how different parts of the brain have developed specific functions over time—such as the ventral area for fundamental survival and the dorsal for more advanced adaptation processes.

The team also discovered that transcription factors, which are proteins that control gene expression, act as a ‘code’ that defines a cell’s identity. Furthermore, the atlas revealed the complex communication network within the brain, facilitated by a variety of signaling molecules. This diversity is essential for intricate interactions among different cell types.

Zeng is confident that the consistency across various datasets—genomic, epigenomic, and spatial—confirms that the atlas does more than just identify cells; it effectively captures the fundamental organizational principles of mammalian brain development.

Looking to the future, this atlas sets a precedent for similar research in other species, including humans, with such studies already in progress. It also offers a blueprint for genetically targeting specific cell types. This capability could revolutionize the study of certain brain functions and diseases, potentially leading to more precise treatments.

Zeng emphasizes, “We know that many diseases originate in specific parts of the brain, and probably in specific cell types. With this map in hand, we can gain a more precise view of the dysfunction of disease and then create genetic or pharmacologic tools to target those specific cell types, to achieve greater efficacy and minimal side effects.”

Source:10.1038/d42859-023-00069-2 / 10.1038/s41586-019-0000-0

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