The human body is composed of trillions of cells. They show great cell diversity and a high degree of spatial organization—a developmental product that is constantly changing due to factors such as environment and age. Understanding the interactions between the complex structure and functional details of our cells is essential for basic and clinical research. However, historically, scientists seeking to explore the elements of biological space were limited by the technology of the time, which prevented them from combining single-cell insights with tissue-wide observations.
Now, in the field of molecular biology called spatial transcriptomics, this obstacle is beginning to disappear.recognized as Best Method of the Year go through nature In 2020, space transcriptomics adopts advanced imaging methods and novel chemical techniques, which will greatly expand our understanding of health and disease.
Location, location, location
To understand disease, we must understand what a healthy body is, where position is very important. During development, all cells carry the same copy of the genome. Over time, cells will differentiate into various types based on clues from their spatial environment. These clues regulate the expression of its genome as needed, leading to different transcription patterns and subsequent protein expression in each cell. In this way, cells acquire a phenotype suitable for their role in the body—for example, as brain cells, liver cells, or muscle cells. In whole organs or tissues, even in smaller microenvironments, different cell types coexist in physical space. Each area contains an interactive community, in the case of acute and chronic diseases, the balance may be lost and cause disease symptoms.
Diseases usually trigger changes in specific cell types or body parts.For example, liver cirrhosis and Several cell types were found there, Neurodegeneration of the brain is considered Partly driven by changes in glial cells, And the microenvironment of cancerous tumors Coordinating the actions of multiple cell types Promote tumor growth and metastasis. Although progress has been made in elucidating the cellular and molecular changes associated with disease, science has only just begun to touch the skin. For diseases that are poorly understood, scientists may not even know what they are looking for. In order to understand these medical problems, scientists need a picture called “Cell Atlas“It provides the location and identity of all cells in the human body based on genetic, transcriptomics, proteomics, and metabolomics characteristics. The work to establish a complete human cell map is still in progress, but scientists are already able to use it. Growing data volume Identify new genetic and cellular characteristics of the disease.
Making these reference pictures is not easy, because they must reflect the enormous complexity of the human body. Spatial transcriptomics represents a powerful cell mapping strategy. It uses high-throughput methods and single-cell technology to enable researchers to start classifying cells into cell types based on RNA expression. Then link this information to cell shape, size, function, and interaction with cell neighbors—all in the context of the entire tissue.
Challenges along the way
Space transcriptomics aims to analyze the astronomical numbers of cells and map the differences between them. Therefore, scientists need technologies that can obtain large amounts of single-molecule data at a certain speed, scale, and sensitivity, which is practical for mapping the entire organism to produce results that can reliably distinguish healthy tissues from diseased tissues.
However, the need for subcellular details and tissue-wide data presents a major challenge to the field. In order to meet these two needs, spatial transcriptomics technology must maximize some key capabilities: the size of the tissue area that can be analyzed in each experiment, the number of genes that can be evaluated in each experiment, detection efficiency, and spatial resolution. picture. However, so far, most spatial transcriptomics solutions have been forced to compromise the quality of one or more of them for other functions. On the other hand, although many single-cell sequencing technologies on the market provide the advantage of performing genetic analysis on many genes at once, these methods will lose all spatial information by breaking down tissues.
The future of spatial transcriptomics
Certain biological problems, such as those involving atlasing the entire organs of healthy and diseased individuals to discover biomarkers of the disease, are currently impossible for most laboratories to achieve. However, advances in this field are expected to improve our capture of genome-scale transcriptome data and reduce costs, and will soon carry out routine experiments that were unimaginable before. This is because new space technologies are integrating more functions to improve the quality of available data, such as:
- Multiplex analysis-each experiment detects hundreds or more mRNA types
- Resolution-single-cell/sub-cell resolution, providing insight into the location and copy number of mRNA types
- Sensitivity-identify cells with low gene expression
- Sample area-can analyze and capture the entire slice of tissue structure and a large number of cells
Next-generation spatial transcriptomics tools should perform well in every aspect of these functions without sacrificing the quality of other functions. This will enable scientists to thoroughly understand how cells follow a unique spatial organization, which is the basis for their function, classification, and influence on neighboring cells. Through new spatial data, scientific models of biological systems will be rooted in accurate and detailed maps of actual biological tissues, providing unparalleled insights into biological systems. With these maps, the disease can be solved not only according to its molecular mechanism, but also through a systematic understanding of its etiology. The development of space technology will not only provide researchers with increasingly transformative insights into organization-scale basic research and translational medicine, but will also accelerate drug discovery and development.
Photo: Lonely…, Getty Images
