After the completion of the Human Genome Project (HGP), which involved scientists from six countries, we initially grasped the genetic "codebook". However, genetic information is carried by cells, but to this day, humans have not been able to get a glimpse of their own cell map.
Comprehensively decoding the digital characteristics of cells will promote life science research and provide basic resources and tools for the development of biomedicine. A new study, led by the Huada Life Science Research Institute in Shenzhen, has set its sights on macaques, which are genetically similar to humans, and mapped a cell map of the whole body organs of macaques. It is also the world's first non-human primate whole cell atlas.
The study was published online on the evening of April 13 in the top academic journal Nature, titled "Cell transcriptomic atlas of the non-human primate Macaca fascicularis." The research was conducted by 35 research teams from 6 countries, including Shenzhen BGI Life Science Research Institute, Beijing Huada Life Science Research Institute, Shenzhen National Gene Bank, Jilin University, Guangzhou Institute of Biomedicine and Health of Chinese Academy of Sciences, Karolinska Institute of Medicine and Health in Sweden, University of Cambridge in the United Kingdom, ICREA Institute in Spain, and ASTAR in Singapore.
"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 established the non-human primate million single-cell interactive resource website NHPCA (https://db.cngb.org/nhpca/).
Liu Longqi, one of the co-corresponding authors of the paper and the Shenzhen Huada Life Science Research Institute, said in an interview with the surging news (www.thepaper.cn) reporter, "From the perspective of genome sequence, the difference between macaque monkeys and humans is much smaller than that of model animals such as mice, which is the first reason for choosing monkeys; second, if you want to really understand human diseases, such as Parkinson's, Alzheimer's disease, etc., you can't do research directly on humans, we must build animal disease models. Non-human primates, in particular, have significant advantages in the study of cognitive and neurological disorders. ”
Liu Longqi said that at present, there is less such data, and macaques are still a blank, "so the release of these data is very important for a series of studies in the future, including understanding the disease mechanism and drug screening." ”
It is worth mentioning that based on this map, the research team also built a virus database containing 126 virus-susceptible cell types such as new crown, hepatitis B, and rabies virus, which is like a "virus dictionary" that can quickly query the cell types most likely to infect the virus and see the organs that the cell type may be distributed.
The research team believes that with this "virus dictionary", doctors may also check the kidneys, liver and gallbladder at the same time when examining the lungs of patients diagnosed with new crown pneumonia. 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.
"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." ”
Crab-eating macaque cell atlas.
It is worth mentioning that the mapping of this cell map is inseparable from the advancement of single-cell sequencing technology and the decline in sequencing costs. Liu Longqi introduced that technology and cost constraints are also an important reason for the current progress of the Human Cell Atlas program.
Human Cell Atlas is an international big science program that has emerged in the field of life sciences in recent years, and was proposed by scientists such as the United Kingdom and the United States in 2017. In the long term, the program aims to describe the detailed characteristics of each cell (about 37 trillion) in the human body, present the 3D structure of different types of cells in human tissue, outline the interconnections of all human systems, and reveal the relationship between grammatic changes and health and disease. The Human Cell Atlas program will radically improve people's understanding, diagnosis and treatment of disease.
Liu Longqi believes that BGI was able to map macaque cells on a large scale, and the preliminary preparation mainly lies in the breakthrough in tools, "so that we can really open up the sequencing from upstream library construction to downstream." According to the research team, at present, based on BGI's self-developed single-cell library building platform (DNBelab C4) and DNBSEQ sequencing technology, experts and researchers in the field can conduct large-scale single-cell sequencing analysis with low cost, high throughput, high sensitivity and accuracy.
Thesis link: https://www.nature.com/articles/s41586-022-04587-3