On July 12, 2023, a research paper presenting the most comprehensive primate cerebral cortex cell types and their molecular characteristics to date was published in Cell, setting a new milestone for the development of neuroscience. 

This research was jointly conducted by over 100 interdisciplinary researchers from various institutions, including the Center for Excellence in Brain Science and Intelligent Technology of the Chinese Academy of Sciences, BGI-Research, and others.

Following the publication of this research, the researchers shared their insights on this study and addressed some intriguing questions regarding future research.

Q: How should we interpret the significance of the current macaque brain map achievement for future neuroscience research?

Poo Muming: 

(Academician of the Chinese Academy of Sciences, Scientific Director of Institute of Neuroscience, Chinese Academy of Sciences, and CAS Center for Excellence in Brain Science and Intelligence Technology)

Identifying various types of single cells is a necessary condition for studying both structural and functional maps. Once we determine the cell types, we can label and track their connections, enabling the completion of comprehensive connectivity maps among different cell types.

On top of these, there is also a third type of map, which is the functional map. Once we have the connectivity map, the next step is to study the dynamic functions that arise from these connections. Therefore, the future research plans will keep increasing, and as Director Xu (Xun) (of BGI-Research) mentioned, what we have accomplished this time is just the beginning.

We can imagine that the research on the entire brain needs to reach the functional level. This is a very lengthy process, and it may not be completed even by the end of this century. Therefore, neuroscience is the ultimate frontier of our present century.

Q: What groundbreaking achievements have been made in this research?

Sun Yidi:

(Co-corresponding Author of the study, Junior Researcher at the Center for Excellence in Brain Science and Intelligent Technology of the Chinese Academy of Sciences) 

We know that the brain of primates is quite large, with different brain regions responsible for the implementation of various complex functions. Previously, there was no such technological means to achieve large-scale, high-throughput transcriptome data mapping. For the first time, our research has achieved the mapping of gene expression and cell types in 143 brain regions of the macaque cerebral cortex.

In this research, we have also generated the most comprehensive database of cell types and gene expression in the macaque cerebral cortex currently available in the world. We have transformed this data into an online website, making it convenient for scientists worldwide to share and utilize.

Q: Based on this research, what directions will the research team focus on in the future?

Li Chengyu:

(Co-corresponding Author of the study, Researcher at the Center for Excellence in Brain Science and Intelligent Technology of the Chinese Academy of Sciences)

One direction of our research is related to the human brain, because ultimately, we aim to address brain-related diseases such as Alzheimer's, depression, and Parkinson's disease. Currently, there is an urgent need to identify potential therapeutic targets for these diseases. The identification of novel targets is a crucial indicator for the leading position in the field of biomedicine. We believe this is an essential area that requires concerted efforts and collaboration from our research team.

The second direction is to understand how the brain is formed, and a crucial aspect of understanding the brain lies in studying its evolution. Evolution is a fascinating field, and I believe it plays a significant role in our future understanding of the brain. It can be said that comprehending the origin of our intelligence is a crucial issue that will greatly contribute to our understanding of the brain.

Q: What was the opportunity for this collaboration with BGI?

Li Chao: 

(Co-first Author of the study, Director of the Single-cell Platform at the Center for Excellence in Brain Science and Intelligent Technology of the Chinese Academy of Sciences)

In the early stages of our research, we conducted some single-cell sequencing experiments on macaque. After the release of the spatial-temporal omics technology developed by BGI, we identified several collaboration opportunities that allowed us to utilize this new proprietary Stereo-seq technology to gain a deeper analysis of the macaque brain atlas. By combining Stereo-seq technology with large-scale analysis, we have achieved a pioneering result both globally and in China.

Q: What role did AI algorithms play in this research?

Yao Jianhua:

(Co-corresponding Author of the study, Chief Scientist of AI Medical at Tencent AI Lab)

The Stereo-seq technology adopted in the macaque brain research is the most advanced technology in the world. Its main features include large field of view and high resolution, which produces great amount of data. Conventional data analysis methods struggle to handle such massive datasets. Therefore, we require more advanced AI algorithms to effectively analyze this data.

Our AI Lab focuses on two main tasks: cell localization and cell characterization. These tasks leverage our previous expertise and accumulation in image analysis and gene data analysis.

Read more about this research:

https://en.genomics.cn/en-news-6760.html