On the evening of May 4th, Shenzhen Huada Life Science Research Institute (hereinafter referred to as BGI Research Institute) and a number of institutions released the world's first batch of spatio-temporal maps of life on the official website of Cell Publishing House in the form of spatiotems alliance (STOC) topics. 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.
Screenshot of the feature page on cell publishers' official website
Using BGI's self-developed spatiotemporal omics technology Stereo-seq, which can be called the "ultra-wide-angle excipient pixel life camera", the researchers first mapped the spatio-temporal map 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.
Mouse spatiotemporal atlas published in Cell
Spatio-temporal atlas of zebrafish, fruit flies, and Arabidopsis thaliana published in Developmental Cells
Stereo-seq technology can simultaneously "shoot" the genetic information and spatial position of each cell in the tissue, using a chip based on BGI's self-developed DNBSEQ sequencing technology, an array-arranged DNA nanosphere space capture chip with spatial position information. 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.
"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.
Space-time chips used in Stereo-seq technology
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, an international scientific alliance composed of more than 80 scientists from 16 countries, including 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 Space-Time Omics Alliance, including 1 Cell article, 3 Developmental Cell and 4 pre-printed articles.
The human body has 37 trillion cells, 100 times the number of stars in the Milky Way. In the past, however, we knew very little about how these cells make up a complex organism.
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. Today, Stereo-seq technology not only allows us to precisely understand the molecular expression within each cell, but also to locate the spatial location of that cell. If we compare the human body with 37 trillion cells to the Earth on which we live, the previous technology may allow us to understand what creatures are on the planet, and the Stereo-seq technology allows us to see which country, which region, which city each organism is distributed in, and what they are doing, how they communicate with other species, and even, see their past and future.
High-precision panoramic cellular resolution mouse embryo map
"The emergence of spatiotem-time omics technology has realized the comprehensive mapping of the cell 'map' of life in the temporal and spatial dimensions, allowing 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, and 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." 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, said.
The researchers used this "ultra-wide-angle 10-billion pixel life camera" to "take" 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 in mouse embryos and the formation of cell evolution. 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 level of single-cell resolution, providing an important data reference for mammalian development studies, promoting our better understanding of embryonic growth and organogenesis, and providing guidance for research related to birth defects.
Spatiotemporal atlas of mouse embryos at days 9.5-16.5
Robinow syndrome is a typical birth defect that is clinically manifested as abnormal facial and limb development (such as cleft lip and palate), and a gene associated with it has been clinically identified, but how this gene causes these abnormalities is unknown. The researchers located the relevant genes in the process of mouse embryonic development, and found that there was a specific high expression of the gene in the lips, palate and toes of mice, indicating that this gene is very important in the development of the lips, palate and toes of mice, which explains why many patients with Robinow syndrome have a cleft lip and palate and short limbs.
"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, co-author of the Cell paper and dean of the School of Clinical Medicine at the University of Cambridge in the United Kingdom. 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. ”
"The amount of data required for spatiotem omics techniques has increased by an order of magnitude compared to past omics techniques, which is an unprecedented challenge. To this end, we have developed a series of new algorithms and related visualization databases adapted to its data analysis, hoping to help solve a series of challenges that may be faced in the field in the future in terms of computing storage and algorithmic computing power. Li Yuxiang, one of the co-corresponding authors of the series of papers and chief scientist of bioinformatics at the Shenzhen Huada Institute of Life Sciences, mentioned.
In addition to mice, the researchers also studied the development process of zebrafish, fruit fly and other model organisms, and constructed a spatiotemporal map of the embryonic development of zebrafish and fruit fly, which provided important data reference for the pattern formation and related molecular mechanisms in the embryonic development process, and also provided a possibility 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.
In addition, the special webpage also displays 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.
"The progress of life sciences depends on the development of technology, and in the future, we will further develop spatiotem technology for clinical samples and space-time multi-omics technology, which we believe will bring important impetus to life sciences and medical research." Xu Xun, another co-corresponding author of the series of papers and president of the Shenzhen Huada Institute of Life Sciences, said, "The mapping of life space-time is inseparable from the cooperation of global scientists in the organizational mode of big science and engineering, and through the space-time omics alliance, we will work together with scientists in various fields in the future to promote the comprehensive development of organ maps, disease pathology, ontogenesis and life evolution." ”
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. The research has passed the ethical review and strictly follows the corresponding regulations and ethical guidelines.