Single-cell RNA sequencing (scRNA-seq) methods can help better our understanding of disease and immunology. This method provides unparalleled opportunities to investigate cell populations at the single cell level to identify rare cell types, changes in cell phenotypes and study disease progression in novel epidemics such as Ebola and the current COVID-19 virus. The knowledge derived from such studies can then help in developing therapeutic strategies, treatments or vaccines.
The Nadia instrument, using microfluidics technology, permits high throughput single cell experiments such as scRNA-seq while the Nadia innovate platform gives scientists the flexibility to develop new single-cell applications. Both platforms can be used to encapsulate cells of widely varying sizes, from tiny bacterial cells to macrophages and other large human cells.
In a recent publication, Cribbs et al. studied the role of histone H3K27me3 demethylases KDM6A/B in regulating T cells. The authors used the Nadia instrument, to perform scRNA-seq on T cells, revealing important cell heterogeneity and identifying highly inflammatory memory cells and resting cells. These results suggest that targeting and inhibiting KDM6 demethylases could be an interesting therapeutic strategy for autoimmune disease (Cribbs et al. 2020). In this context, the information provided by the single cell resolution is critical for ongoing drug development. Read more about it here.
By enabling the co-encapsulation of two or more single cells, droplet-based microfluidics allow the study of immune cell-cell interactions. Taken to the single-cell level, the heterogeneity observed amongst immune cells, clinical tissue samples or pathogen populations can be explored in unprecedented detail.
The unrivalled versatility of the Nadia Innovate makes this system highly suited to implement such methodologies. For example, it offers the possibility to embed cells in agarose beads for prolonged 3D growth studies and imaging of co-encapsulated cells. With the Nadia Product Family, understanding long term single cell immune responses is no longer relegated to cumbersome well-plate methods with limited throughput.
Infectious diseases remain a leading cause of mortality worldwide. Whilst acquired or active immunity is a product of immune responses, passive immunity consists in the direct injection of antibodies into an organism that is already infected, supplementing the body’s natural immune response, rather than stimulating it. Building on the high-throughput and versatile encapsulation methods of the Nadia Innovate platform, protocols can be developed to screen for suitable antibody producing cells. With precise encapsulation of single immune cells with fluorescence detection reagents in hardened hydrogel beads, selective fluorescent sorting can recover antibody-producing cells along with their secreted factors of interest.
With the Nadia Innovate, complex multistep screening, production and selective immunity techniques are at the user’s fingertips, limited only by imagination.
Cribbs, Adam P., Stefan Terlecki-Zaniewicz, Martin Philpott, Jeroen Baardman, David Ahern, Morten Lindow, Susanna Obad, et al. 2020. ‘Histone H3K27me3 Demethylases Regulate Human Th17 Cell Development and Effector Functions by Impacting on Metabolism’. Proceedings of the National Academy of Sciences, March. https://doi.org/10.1073/pnas.1919893117.