From Sample to Discovery: The Impact of High-Quality Nuclei Isolation on Research Outcomes

As scientists understand more about complex diseases, they are increasing turning to single cell genomic assays to help them identify new potential therapeutic targets. One essential step in single-cell and multiomic research is tissue dissociation—transforming complex tissue structures, often from rare and precious clinical samples, into high-quality single-cell or single-nuclei suspensions.

Achieving consistent cell or nuclei isolations in this step can significantly affect downstream applications, especially for complex studies aimed at identifying therapeutic targets. Automated tissue dissociation systems, like the Singulator Platform^TM, enable researchers to perform consistent and reproducible nuclei isolation, paving the way for accelerated discoveries and better outcomes.

 The Importance of Automated Tissue Dissociation and Nuclei Isolation

Effective tissue dissociation is the foundation of high-quality single-cell and single-nuclei analyses. Manual processes for tissue dissociation can lead to variability, reduce reproducibility, and slow down discoveries. By contrast, automated tissue dissociation offers researchers a way to achieve uniform results by standardizing steps, reducing hands-on time and minimizing opportunities for error or bias. The Singulator Platform is at the forefront of this shift, providing researchers with a reliable, automated solution that isolates high-quality single cells or nuclei from various tissue types with precision and reproducibility.

How the Singulator Platform Advances Research and Accelerates Discoveries

With automated tissue dissociation, researchers can avoid some of the time-consuming and error-prone steps associated with manual workflows. As highlighted in these recent studies, the Singulator Platform is becoming an essential tool to streamline sample preparation for single-cell analyses. Here’s a closer look at the impact of the Singulator Platform, as demonstrated by recent research:

1. Causal Gene Identification in Atrial Fibrillation by single-cell multiomics: Researchers from three continents collaborated in a recent study published in Circulation  to determine the causal genes in atrial fibrillation.  They employed the Singulator Platform to isolate a nuclei suspension from human left atrium appendages, a tissue known to be associated the formation of clots in patients with atrial fibrulation¹.  Next, they performed single-cell Multiome (scMultiome), a method that pairs single-cell RNA-Sequencing (scRNA-Seq) and single-cell Assay for Transposase-Accessible Chromatin sequencing (scATAC-seq).  These data were used to implicate 14 genes at 9 Atrial Fibrillation GWAS loci. Finally, the authors determined that CRISPR inactivation (CRISPRi) in human embryonic stem cells-derived cardiomyocytes of the strongest Atrial Fibrillation associated gene, can dysregulate the pathways linked to the development of atrial tissue and the cardiac conduction system².  Taken together, scientist have 9 new targets to investigate for life saving therapies.
2. Revolutionizing Heart Disease Treatment with snRNA-Seq: Scientists at University of Tokyo used the Singulator Platform to isolate nuclei from patients diagnosed with dilated cardiomyopathy with severe heart failure and control subjects.  They found that Igfbp7 (insulin like growth factor 7) is upregulated in senescent endothelial cells (ECs), and insulin signaling and oxidative phosphorylation are downregulated in patients with failing hearts when compared to control patients.  These data, combined with data from mouse models, provided the rationale for developing a vaccine against Igfbp7, which ameliorated cardiac dysfunction in a mouse model of heart failure. The authors concluded Igfbp7 produced by senescent ECs can causes cardiac dysfunction.  Furthermore, they demonstrated that a vaccine therapy targeting Igfb7 may be useful in preventing the development of heart failure³.  These authors are developing a novel way to prevent heart disease in at risk patients through the use of vaccination against an endogenous protein that is upregulated in heart disease.
3. Immune Activation Confirmed in Fibrotic Liver by snRNA-Seq:
In the growing field of metabolic research, researchers from the Catholic University of South Korea collaborated with scientists at St Mary’s Hospital to study metabolic dysfunction- associated steatohepatitis (MASH). MASH is a liver disease that is likely caused by innate immune system activation.  These researchers demonstrated how the Singulator Platform facilitates the isolation of high-quality nuclei from healthy and fibrotic liver, enabling them to investigate innate immune cell populations with greater accuracy. By automating the process, they achieved consistent nuclei preparations that enabled them to measure an increase in macrophages in fibrotic livers and then develop a high-resolution gene expression map of the innate immune response by cell type. These discoveries support Chitinase 1 as a therapeutic target for the treatment of MASH by modulating the innate immune response.

In all 3 publications, the authors chose to forego optimizing tissue dissociation and nuclei isolation by manual methods in favor of the ease of use and consistency that the Singulator Platform provides.

Enabling Precision with Automation

Each of these studies underscores a common theme: the Singulator Platform’s automated approach to tissue dissociation and nuclei isolation supports more efficient workflows and higher-quality results. By minimizing variability and delivering reproducible samples, researchers can focus on data analysis and discovery rather than troubleshooting manual preparation steps. For laboratories aiming to keep pace with the demands of modern research, automated tissue dissociation is no longer a luxury; it’s a necessity.

Conclusion: A Path to Faster Therapeutic Discoveries

The precision and consistency of automated tissue dissociation and nuclei isolation have set a new standard for sample preparation. By eliminating the variability associated with manual processes, the Singulator Platform enables scientists to unlock insights faster and more accurately, ultimately helping to identify therapeutic targets that could lead to life-changing treatments. For researchers looking to expedite their workflows and enhance the quality of their outcomes, the Singulator Platform represents a powerful ally on the path from sample to discovery.

Automating tissue dissociation and nuclei isolation doesn’t just save time—it shortens the time to insight, advancing science and supporting discoveries that can make a real impact. As demonstrated in these studies, adopting the Singulator Platform can be a game-changer in achieving reliable, high-quality nuclei preparations.

References

1. https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/left-atrial-appendage-closure-procedures
2. Leblanc, FJA, et al. Atrial fibrillation variant-to-gene prioritization through cross-ancestry eQTL and single-nucleus multiomic analyses, iScience, 2024 Aug 5;27(9):110660. doi: 10.1016/j.isci.2024.110660. eCollection 2024 Sep 20.
3. Katoh, M et al. Vaccine Therapy for Heart Failure Targeting the Inflammatory Cytokine Igfbp7, Circulation, 2024 Jul 30;150(5):374-389. doi: 10.1161/CIRCULATIONAHA.123.064719.
4. Cha JH et al. Chitinase 1: a novel therapeutic target in metabolic dysfunction-associated steatohepatitis, Front Immunol 2024 Sep 23:15:1444100. doi: 10.3389/fimmu.2024.1444100. eCollection 2024.