Scientists from Leipzig University and Helmholtz Munich have developed a new, cost-effective method to analyze rare cell types, cell communication types, and disease patterns in tissue, according to their findings published in the journal Nature Communications.
The new method combines imaging and sequencing techniques and uses a microfluidic chip to obtain spatially resolved genomic data paired with high-quality microscopy images. The team increased the amount of image information per pixel by a factor of six or twelve, enabling the visualization of rare cell types in the kidney or liver.
In addition to the new method, the team also provided an open-source analysis pipeline to make it easily accessible for researchers. This makes the methodology more suitable for a wide range of tissues, which is beneficial for studies of complex diseases and multi-organ functions and dysfunctions.
This workflow builds on the development of single-cell sequencing methods that have made it possible to better understand cellular developmental pathways and disease progression. Spatially resolved transcriptomics of tissue sections enables advances in fundamental and applied biomedical research. The combination of imaging and sequencing techniques was a vision until recently, and it has revolutionized the understanding of cellular heterogeneity, allowing researchers to find new cell types in all organisms.
This new protocol overcomes the limitations of tissue dissociation protocols that cause loss of spatial information and alteration of cell type proportions. The scientists developed spatial transcriptomics (ST) based on imaging, sequencing, or a combination of both methodologies, which enables the detection of mRNAs of the whole transcriptome rather than just a predetermined set of genes.
The method's functionality was demonstrated by acquiring 16 spatially resolved transcriptomic datasets from five different murine organs, including the cerebellum, liver, kidney, spleen, and heart. Factor analysis and deconvolution of spatial transcriptomes allowed for in-depth characterization of the murine kidney.
The new method is a significant step forward in understanding complex diseases, as well as multi-organ functions and dysfunctions. Its ability to detect new or unique cell types will undoubtedly help scientists advance biomedical research and potentially lead to new treatments and cures for diseases.