New single-cell method enhances the treatment of complex diseases
Understanding how genes are switched on or off in individual cells is crucial for uncovering the mechanisms that drive immune responses, cell development, and disease. Technologies that measure gene expression (RNA) and chromatin accessibility – i.e., how “open” or “closed” regions of the genome are – at single-cell resolution have already transformed biology. However, until now, these methods have been limited by high costs and scalability issues, restricting their use in large-scale studies.
Researchers have now developed a new method, SUM-seq, which builds on existing technologies by introducing a multiplexing strategy that drastically increases throughput while reducing costs. It allows researchers to study cellular responses over time or under different conditions using fixed or frozen samples – an especially valuable feature for clinical and collaborative studies.
Case studies conducted during the research demonstrated that SUM-seq can uncover complex gene regulatory programs that govern cell behavior, development, and responses to disease-relevant signals.
Genome-wide association studies have shown that most disease-associated variants are located in non-coding regulatory regions of the genome. Therefore, understanding how these regions control gene expression and cellular function is essential.
“Multiomic single-cell sequencing, which measures both chromatin accessibility and gene expression, enables researchers to decipher the relationship between regulatory regions and gene activity. However, these relationships are highly dynamic and context-dependent, requiring data from a broad range of relevant samples or conditions – something not feasible with current methods”, says Mikael Marttinen from Tampere University.
“SUM-seq addresses this need by dramatically increasing the throughput of multiomic single-cell sequencing while reducing costs. This makes the technology suitable for large cohort studies, complex experimental designs, and more accessible to smaller research initiatives”, he adds.
As a result, SUM-seq opens new possibilities for large-scale screens, organoid-based disease models, and multi-center clinical studies, ultimately contributing to a better understanding and treatment of complex diseases.
The article "Single-cell ultra-high-throughput multiplexed chromatin and RNA profiling reveals gene regulatory dynamics" was published in Nature Methods on 26 May 2025.
