Study by Vilnius University Life Sciences Center Published in Science Marks a New Era in Single‑Cell Research

A study led by a team of scientists from the Life Sciences Center of Vilnius University (VU LSC), published in the prestigious journal Science, introduces a novel technology that fundamentally expands the possibilities of genetic research at the single-cell level.

The article presents a universal semi-permeable capsule (SPC) technology designed for high-throughput single-cell omics – research methods and tools that enable the simultaneous probing of multiple layers of biological information encoded within individual cells in a single experiment. This technology makes it possible to perform parallel profiling of cellular phenotype and genotype, maintain cell viability, form cellular spheroids, conduct multi-step biochemical reactions on genetic material from individual cells, and offer a range of additional analytical advantages.

Notably, the VU research team has demonstrated that SPCs are not limited to a single application, highlighting the broad practical potential of this technology. As part of the study, the researchers developed and applied a new RNA sequencing method, CapSeq (Capsule-based RNA Sequencing), which enables the analysis of genetic information from more than 100,000 individual cells in a single experiment, allowing for the identification of malignant cells based on altered gene expression patterns.

‘In this work, we show that SPCs can serve as a universal platform for single-cell transcriptomics and genomics. This technology enables the targeted selection of rare or clinically relevant cells to address key biological questions,’ emphasised first author Denis Baronas, a doctoral student at VU LSC.

‘Crucially, cells encapsulated in SPCs remain viable and functional for extended periods, which is not possible with microfluidic technologies. Within the capsules, we can monitor cells, culture them for weeks, sort them, and only then decide which genetic or molecular analyses to perform,’ noted Prof. Linas Mažutis from the Institute of Biotechnology of VU LSC.

Solving a decades-old challenge

The newly developed SPC method addresses a long-standing challenge: how to efficiently and cost-effectively profile both cellular function and the biological information encoded in the genome. Such analyses often require multiple sequential enzymatic or biochemical reactions, which may be incompatible with one another due to differences in pH, temperature, salt concentration, or other conditions. Until now, researchers have been forced to choose between high-throughput droplet-based technologies, which are limited to single-step biochemical reactions, or low-throughput, multi-step reactions performed in test tubes or 96-well plates.

‘Single-cell research is one of the most important directions in modern biology and medicine, yet it has long required a trade-off between high throughput and flexibility. Our technology brings these two aspects together,’ said Prof. Mažutis.

The SPC technology is based on microscopic hydrogel capsules that encapsulate individual cells. With a diameter of approximately 70 µm, up to a million single cells can be maintained and analysed within a single laboratory tube. The capsules function as a selective sieve, allowing nutrients, enzymes, and molecular reagents required for molecular analyses to pass through, while retaining genetic material – DNA and RNA – inside the capsule after cell lysis. This key feature enabled the VU team to develop CapSeq – a single-cell RNA sequencing method that supports efficient multi-step biochemical reactions and prepares cells for transcriptomic profiling (i.e. determining which genes are active, in which cells, and to what extent).

Unveiling what was previously invisible

In their Science article, the researchers showcase the capabilities of the SPC technology through a study of acute myeloid leukaemia (AML). Using CapSeq, the team was able – for the first time – to reliably profile circulating blast cells in patients with distinct mutational backgrounds and to assess granulocyte-specific responses to AML-induced physiological changes.
The study revealed substantial cellular diversity, enabled more precise correlations between molecular cell profiles and disease prognosis, and demonstrated that even seemingly ‘healthy’ immune cells in AML patients are already influenced by disease processes.

‘Our research reveals a striking insight: as blood cancer progresses, the immune system undergoes profound reprogramming. Even cells that appear healthy are affected by disease and inflammatory processes. We hope that our findings will contribute to the development of new diagnostic tools and support more precise, personalised treatment strategies in the future,’ stated Prof. Mažutis, research lead.

Publication in Science represents a major academic achievement. Alongside Nature and Cell, Science is regarded as one of the world’s most prestigious scientific journals, known for its exceptionally rigorous peer-review standards.

‘This confirms that innovations developed at the Life Sciences Center of Vilnius University can proudly compete with those of the globe’s leading research institutions. We’re no longer just users of advanced technologies – we’re the ones creating them. CapSeq was developed here in Vilnius and is now set to become a tool for scientists worldwide,’ said Dr Arvydas Lubys, Director of VU LSC.

Future prospects

Capsule-based single-cell genomics and transcriptomics are not limited to cancer research and can be readily applied to the study of a wide range of complex diseases. Cells encapsulated in SPCs can be frozen and thawed, cultured for weeks, and sorted based on gene expression markers – opening new opportunities for clinical studies using valuable patient samples and advancing personalised medicine.

The technology is expected to become one of the core services of the Translational Gene Technology Centre at VU LSC, scheduled to open in 2026, which will provide high-level research services to academia and industry across the region.

The authors note that the capsule technology presented in Science is currently undergoing patenting, and active efforts toward commercialisation are underway.

It is also noteworthy that the same issue of Science features another article with Ignas Maželis, a graduate of Vilnius University, as first author. In 2021, at the initiative of Prof. Mažutis, he began his doctoral studies at Harvard University.

Authors of the Science publication:

Denis Baronas (VU LSC), Simonas Norvaišis (VU LSC), Justina Žvirblytė (VU LSC), Greta Leonavičienė (VU LSC; ‘Atrandi Biosciences’), Vincenta Mikulėnaitė (VU LSC), Karolis Goda (VU LSC), Vytautas Kašėta (State Research Institute Innovative Medicine Centre), Karolis Šablauskas (Hematology, Oncology and Transfusion Medicine Centre of Santaros Klinikos (VU Hospital); National Cancer Center; VU Santaros Klinikos; VU Institute of Data Science and Digital Technologies), Laimonas Griškevičius (Hematology, Oncology and Transfusion Medicine Centre of VU Santaros Klinikos; National Cancer Center; VU Santaros Klinikos; Institute of Clinical Medicine of the VU Faculty of Medicine), Simonas Juzėnas (VU LSC), and Linas Mažutis (VU LSC).

The research was conducted as part of the TRACEGET project.

More information can be found here (available in Lithuanian).