On the evening of April 13, Beijing time, the first non-human primate (macaque) whole-body organ cell atlas led by Shenzhen Huada Institute of Life Sciences and jointly participated by multinational scientific research teams was published in the international top academic journal Nature. The atlas will be used for research related to species evolution, human diseases, and drug evaluation and screening, providing basic resources and tools for the development of biomedicine, providing assistance for disease diagnosis and treatment, targeted drug development, and providing the possibility for humans to better explore the evolution of life.
At the beginning of the 21st century, the advent of the human genome sketch composed a life "book" for life science research, providing a foundation for the digitization of life. However, genetic information is carried by cells, at present, human understanding of their own cells is still very limited, comprehensive decoding of the digital characteristics of cells will promote the research of life sciences, providing basic resources and tools for the development of biomedicine. To this end, the researchers set their sights on macaques, which are genetically similar to humans, and mapped a cell map of the macaques' whole body organs.
"This map is like a 'map', and with it it is equivalent to having a high-precision instrument that explores the resolution of living cells, can 'see' which cells are in each organ, and can also be fine-grained to the specific molecular characteristics of each cell and the interaction with other cells." Dr. Han Lei, the first author of the paper and a graduate student of Shenzhen Huada Life Science Research Institute, said, "This lays a foundation for us to better understand the basic structure of life, explore the relationship between diseases and cells, and provide a new direction for the precision treatment of diseases." ”
Based on BGI's self-developed single-cell library and sequencing platform, the research team conducted single-cell sequencing analysis of about 1.14 million cells in 45 organs of adult macaques, divided them into 113 major cell types and 463 cell subclasses, and built a million single-cell interactive resource website for non-human primates.
Screenshot of the Non-Human Primate Million Cell Interactive Resources website
"Non-human primates have significant advantages over other model animals in the study of human diseases, especially cognitive and neurological diseases," said Liu Longqi, one of the paper's co-corresponding authors and shenzhen Huada Institute of Life Sciences. ”
Provides direction for organ damage repair
There are many common cell types in the tissues of our bodies, which have different molecular characteristics depending on the tissue environment in which they are located. For example, the liver and kidneys may have the same type of cells. Using the non-human primate cell atlas, the researchers found common cell types and their "specific markers" (specific marker genes) of individual tissues, which provide molecular-level evidence for understanding that these common cells perform different functions in different tissues.
At the same time, the researchers also found a variety of cells with differentiation potential present in various tissues, which may provide a cell source for the repair of various organ damages in the future, and provide new ideas for the study of mammalian tissue regeneration.
For the prevention and treatment of viral infectious diseases
and genetic diseases to provide data support
Based on this atlas, the researchers built a virus database containing 126 virus-susceptible cell types such as COVID-19, hepatitis B, and rabies viruses, which is like a "virus dictionary" that can quickly query the cell types most likely to infect the virus and see the organs that are likely to be distributed by that cell type. With it, doctors may also check the kidneys, liver, and gallbladder at the same time when examining the lungs of patients diagnosed with COVID-19. Because the "virus dictionary" mentions that these organs also have cells that may be infected by the new crown virus.
In addition to virus-induced diseases, researchers can also enter pathogenic genes or genetic loci for a particular genetic disease to query the type of possible pathogenic cells for that disease.
Helps reduce drug development time
As we all know, drug development is expensive and time-consuming. The first step, drug primaries, involves screening thousands of drugs for a few relatively effective drugs, which takes a very long time and researchers can't test each drug on animals.
Through this cell map, researchers can target the targeted cell, detect the cell's response to these drugs, so as to quickly select several effective drugs, and then test them on animals. This will greatly shorten the time of large-scale drug screening, and facilitate the development and precision treatment of targeted drugs.
"Large-scale cell mapping is of great significance for our understanding of organ structure, embryonic development and aging, human disease and the evolution of life. In the future, we will also develop higher-throughput single-cell technology and multi-omics technology with spatial resolution, providing an important tool for comprehensively constructing the spatiotemporal map of single-cell resolution of life. Xu Xun, one of the co-corresponding authors of the paper and president of the Shenzhen Huada Life Science Research Institute, said, "At the same time, cell map data is growing rapidly, which contains a huge amount of information, and the interpretation and mining of these data requires the joint collaboration and efforts of scientists around the world." ”
The mapping of this map is inseparable from the advancement of single-cell sequencing technology and the decline in the cost of sequencing. In the past, drawing such a "map" required a lot of time and high experimental costs. Today, based on BGI's self-developed single-cell library building platform (DNBelab C4) and DNBSEQ sequencing technology, domain experts and researchers around the world can perform large-scale single-cell sequencing analysis in a low-cost, high-throughput, high-sensitivity and accurate method, providing a series of valuable data resources for the entire life science field.
The study was conducted by 35 scientific research teams from 6 countries, including Shenzhen Huada Life Science Research Institute, Beijing Huada Life Science Research Institute, Shenzhen National Gene Bank, Jilin University, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Karolinska Institute of Medicine and Health, University of Cambridge in the United Kingdom, ICREA Research Institute in Spain, and ASTAR in Singapore. Han Lei, Wei Xiaoyu, Liu Chuanyu, Zhuang Zhenkun, Zou Xuanxuan, Wang Zhifeng and Giacomo Volpe are the co-first authors of the paper, and Liu Longqi, Xu Xun, Hou Yong and Miguel A. Esteban are the co-corresponding authors of the paper. This study has passed the ethical review and strictly follows the corresponding regulations and ethical guidelines.