Development and advantages of Spatial Transcriptomics
InquiryDevelopment of Spatial Transcriptomics
In the past ten years, the rapid development of transcriptomics technology has mainly gone through three stages. The first research stage was the bulk transcriptome, which allowed to obtain the average gene expression levels of a large number of cells, and although it was important for promoting the understanding of the characteristics of cell populations, it did not allow to know the gene expression of specific cells.
The second stage is single-cell transcriptome sequencing, which enables the study of gene expression down to the single-cell level, allowing for in-depth characterization of cell types and revealing cellular heterogeneity. However, gene expression has both temporal and spatial specificity. Temporal specificity can often be addressed by taking samples at different time points and using single-cell transcriptome sequencing techniques. Temporal specificity can usually be resolved by sampling samples at different time and then using single-cell transcriptome sequencing techniques, but the enzymatic digestion of tissues when obtaining cell suspensions for single-cell studies results in the loss of information on the spatial location of tissues.
The development of high-throughput spatial transcriptome technologies in recent years, such as the 10x Genomics Visium spatialomics technology and GeoMx DSP spatialomics technology, has enabled the study of the transcriptome to be advanced to the third stage. The use of this technology allows simultaneous acquisition of gene expression characteristics and spatial distribution data in tissue in situ, further advancing the study of true gene expression in tissue in situ cells. In addition, combining single-cell transcriptome and spatial transcriptome for joint studies can enable the combination of gene expression studies in spatial locations to the ultra-high resolution single-cell level, which has promising applications for cancer, immune, neurological, and developmental fields.
Integrated single-cell transcriptome and spatial transcriptome analysis in cardiovascular research. (BMB Reports. (2020) 53: 393 - 399 )
Advantages of Spatial Transcriptomics Technology
Spatial Heterogeneity
Human tissues are highly complex systems composed of trillions of cells that differ in type, time and space but coordinate with each other to form unique microenvironments that maintain organ function and process information, which in turn determines the identity of the cells. Through continuous research on the molecular basis of human organs, a scientific consensus has gradually emerged that the myriad of cells with different functional types, combined with developmental (temporal) and regional (spatial) differences, constitute the main factors of transcriptional heterogeneity in mammalian organs.
Many major discoveries in the life sciences have been recognized from the close relationship between cells and biological functions. In clinical research, histopathology is often used as a conclusive diagnostic tool, because many diseases are characterized by spatial specificity in tissues, and infectious and inflammatory processes can radically alter the cellular structure in tissues.
The application of high-throughput single-cell sequencing technology has initially revealed the problems of cell life cycle, cell lineage and developmental trajectory. However, spatial heterogeneity remains a thorny issue, as cells lose their spatial location information once they are isolated in the preparation of single-cell suspensions.
Advantages
By combining imaging and sequencing, state-of-the-art spatial transcriptomics can map the location of specific transcripts in tissues and identify the location of expression of specific genes, thus allowing a more comprehensive study of tissues at the molecular level, making it possible to obtain information on the location of gene expression at single-cell resolution.
This technology can provide new perspectives on tissue and gene expression for research in cancer, neuroscience, developmental biology, immunophysiology, and other fields.
Take tumor as an example to illustrate. The brain is the most important and complex organ in mammals. Spatial heterogeneity is crucial as different regions of the brain are organized with different functions and cell types. Early studies revealing causative factors were generally done by histological staining of major biomarkers. Recent studies have used DNA sequencing, gene chips, transcriptome sequencing, and other technical tools to collect high-throughput histological data from different tissue regions of the brain, such as genomics, transcriptomics, and proteomics, for better molecular mapping of the structure of the central nervous system. However, the expression of important genes in specific cell types may be obscured in the detection of mixed cells, thus hindering further studies. Therefore, a more in-depth molecular mapping of the brain is needed, which needs to have higher resolution and needs to integrate transcript-derived location information, such that brain mapping will hopefully eventually reveal the spatial heterogeneity of the complex organ.
Spatial resolution of cell-type-specific gene expression in the human brain. (Neuropsychopharmacology (2019) 0:1–2)
What We Can Do for You?
cd genomics offers a complete workflow for spatial transcriptome sequencing as well as more customized analyses. At the same time, obtaining high-quality graphical reports through the advanced data analysis system we provide will help you to more efficiently understand the intrinsic causes of complex biological mechanisms.
