In a paper published in STAR Protocols, Oregon Health and Science University researchers Haylie Helms and Luiz Bertassoni present a new method for analyzing how tissue composition and spatial relationships affect cell behavior. The new method is tailored for two-dimensional engineered tissues and cell cultures, which are not compatible with standardized embedding and sectioning techniques. This innovation offers a way to further enhance the power of spatial transcriptomics to provide valuable insights into how intercellular interactions influence health and disease.
Single-cell spatial transcriptomics is a powerful technique for analyzing gene expression of individual cells while simultaneously preserving information related to the positioning of the cells within a tissue or organ. The technique combines the high resolution of single-cell RNA sequencing with the contextual information from spatial transcriptomics and has a wide range of applications across biomedical research and drug development.
While spatial transcriptomics provides important insights into cell-cell interactions, interpretation is often made difficult when using embedded and sectioned tissues due to variability between samples and patients. Moreover, the reliance on sectioned tissue samples prevents controlled experiments. In their new method, Helms and Bertassoni have adapted commercially available protocol designed for embedded and sectioned tissues to fit two dimensional biofabricated tissues. The approach provides a flexible way to combine the experimental benefits of engineered tissues and cell cultures with the analytical capabilities offered by spatial transcriptomics.
The new method is ideal for detailed tissues generated using the Biopixlar single-cell bioprinting technology but can also be used for other flat engineered tissues and seeded cells. This approach is made possible by growing and preparing cells directly on the required microscope slides, eliminating the need for sample transfer and sectioning.
Some of the key benefits of this new approach, according to the authors, is that it both preserves the spatial arrangement of cell, while also avoiding sample loss due to sectioning. The method provides exciting new capabilities for researchers to expand the implementation of spatial transcriptomics to reproducible in vitro systems, thereby providing opportunities to gain new insights into spatially driven biological processes and intercellular interactions.
Read the article Protocol for single-cell spatial transcriptomic profiling of cultured cells and engineered tissues without embedding or sectioning, published in STAR Protocols.