The human body has 37 trillion cells, 100 times the number of stars in the Milky Way. In the 17th century, we saw for the first time through the microscope the microstructure of life—the cell. In the 20th century, DNA sequencing technology allowed us to analyze the large molecule of life for the first time, DNA. However, we still know very little about how cells make up a complex organism.
On May 4, Shenzhen Huada Life Science Research Institute (hereinafter referred to as "BGI Research Institute") and a number of institutions jointly released the world's first spatio-temporal atlas of life on the official website of Cell Publishing House in the form of a spatiotems alliance (STOC) topic. This is the first time that the genetic and cellular changes in the process of life development are analyzed with ultra-high precision from the temporal and spatial dimensions, providing a new direction for cognitive organ structure, life development, human diseases and species evolution.
Using BGI's self-developed space-time omics technology Stereo-seq, the research team first mapped the spatio-temporal mapping of embryonic development or organs of mice, zebrafish, fruit flies, and Arabidopsis thaliana. Among them, the results of the spatio-temporal atlas of mouse embryonic development based on the high-precision large field of view Stereo-seq technology were published online in the journal Cell, and the results related to the spatiotemporal atlas of zebrafish, fruit flies and Arabidopsis thaliana were published online in the sub-journal developmental cell of Cell.
The series of studies was jointly completed by Shenzhen Huada Life Science Research Institute and 32 scientific research teams from 6 countries, including Guangzhou Institute of Biomedicine and Health of Chinese Academy of Sciences, Southern University of Science and Technology, huazhong Agricultural University, etc.
It is worth noting that in order to promote the wide application of spatiotemology in various fields of life sciences, BGI Research Institute and other institutions have launched the Spatiotemomics Alliance, which is an international scientific alliance composed of more than 80 scientists from 16 countries such as Harvard University, Cambridge University, and Oxford University. The results of this special topic are the first batch of blockbuster achievements produced by the Space-Time Omics Alliance led by the BGI Research Institute and the Units of the Space-Time Omics Alliance.
The Stereo-seq is called an "ultra-wide-angle exascale life camera." The technology can simultaneously "photograph" the genetic information and spatial position of each cell in the tissue, and the chip used is a spatial capture chip with spatial position information developed by the research team based on the DNBSEQ sequencing technology independently developed by BGI. The chip can achieve ultra-high precision and ultra-large field of view of life molecule imaging, its resolution of up to 500 nanometers (a single cell can be captured by 400 pixels), to achieve subcellular localization. At the same time, the technology can also achieve a large field of view of up to 13 cm x 13 cm, realizing the mapping of molecular cells in the panoramic view of organs and life.
Space-time chips used in Stereo-seq technology.
Using this technique, the research team "took" multiple "photos" every day on the 9.5-16.5 days of mouse embryonic organ formation, and obtained 53 "photos" of 8 periods to form a spatio-temporal map of embryonic development, just like a panoramic map of life, recording the development of organs and the formation of cells in mouse embryos. The world's first systematic and clear atlas of spatial gene expression in mouse organs across periods was constructed.
This is also the first time that spatial gene expression profiles have been analyzed at the single-cell resolution level, providing an important data reference for mammalian development studies.
Spatiotemporal atlas of mouse embryos at days 9.5-16.5.
In addition to mice, the research team also studied the development process of zebrafish, fruit fly and other model organisms, and constructed a spatio-temporal map of zebrafish and fruit fly embryonic development, which provided important data reference for pattern formation and related molecular mechanism studies during embryonic development, and also provided possibilities for the study of embryonic evolution in the evolutionary process.
In order to overcome the long-term problem that researchers have not been able to effectively analyze the molecular characteristics of highly similar cell types in plant leaves, researchers have also successfully developed a single-cell space group technology suitable for plants based on Stereo-seq technology, and applied this technology to the spatial omics of plant leaf cells. This technology will be applied to basic plant science research and crop breeding research, such as the seed development of rice, wheat and corn and the analysis of mechanisms such as drought resistance, high temperature resistance and salt tolerance, so as to contribute to the cultivation of high-yield, high-quality and stress-resistant crop lines.
The above-mentioned special webpage also shows four BioRxiv pre-printed results, including monkey brain spatiotemporal group atlas, salamander brain regeneration spatiotemporal atlas, tumorigenesis process spatiotemporal group atlas, etc., providing a powerful tool for brain science research and tumor research.
"With stereo-seq technology, humans have for the first time achieved the mapping of a panoramic spatio-temporal map of life at a spatial resolution of 500 nanometers. In the past, it took thousands or even tens of thousands of experiments to complete the spatio-temporal map, and now, on the space-time chip independently developed by BGI, it only takes one positioning to achieve. This is a milestone breakthrough for life sciences tools. Chen Ao, the first author of the "Cell" paper and chief scientist of spatiotemomics of Shenzhen Huada Life Science Research Institute, said.
Liu Longqi, one of the co-corresponding authors of the series of papers and chief scientist of single-cell omics at the Shenzhen BGI Life Science Research Institute, also said, "The emergence of spatiotem omics technology has realized the cells of life in the temporal and spatial dimensions' The comprehensive mapping of the map allows us to observe the distribution of molecules and cells and the interaction between cells in normal and disease states under normal and even subcellular resolution, truly realizing the understanding of function from the perspective of high-precision structure, which will greatly promote our comprehensive understanding of the complexity of life and human diseases. ”
"Thanks to the extremely large field of view of stereo-seq technology, researchers can analyze and study tissues at very high resolution and sequencing depth on developing mouse embryos," said Professor Patrick Maxwell, a member of the Space-Time Alliance and co-author of the Cell paper and dean of the School of Clinical Medicine at the University of Cambridge in the United Kingdom.
Maxwell further mentioned, "Using the freely available data from this study, you can really understand how mammals develop, how tissues are made up, and so on. This will also give us insight into the process of development, normal tissue functioning, and disease. ”
Cell feature page link: https://www.cell.com/consortium/spatiotemporal-omics