[BiG Talk] – Deciphering the epigenetic landscape of the brain: Innovations in chromatin profiling with single-cell nano-CUT&Tag
September 26, 2025 @ 14:00 – 15:00 CEST
Dr Marek Bartosovic, Stockholm University
Abstract
Single-cell epigenomic profiling has revolutionized our understanding of regulatory chromatin, transcription factors, and gene regulatory networks. Single-cell ATAC-seq has driven many of these insights by capturing accessible chromatin. However, the function of regulatory elements such as enhancers, promoters or repressors depends not only on DNA accessibility but also on histone modifications and other epigenetic factors.
To overcome the limitations of open chromatin analysis, we developed single-cell based CUT&Tag, an approach that profiles histone modifications at single-cell resolution. Building on this, we introduce nanobody-based scCUT&Tag, an improved technology that, for the first time, enables multimodal profiling of three epigenetic modalities—including open chromatin and two histone modifications—in thousands of single cells simultaneously. By harnessing a novel set of nanobody–Tn5 transposase fusion proteins, nano-scCUT&Tag achieves lower input requirements, generates more fragments per cell, and improves clustering resolution compared with previous methods. Integrating spatial multi-omics approaches with nano-scCUT&Tag further elucidated the spatial organization of epigenetic modifications within tissue architecture. This integration allows for the mapping of interactions between single cells within intact tissues at a genome-wide scale, providing deeper insights into the spatial context of gene regulation.Using nano-scCUT&Tag on the juvenile mouse central nervous system, we uncovered unprecedented epigenetic heterogeneity. These multimodal profiles facilitate the deconvolution of distinct cell identities in the brain and yield high-quality epigenetic datasets. Furthermore, we applied nano-scCUT&Tag to study chromatin dynamics during an in vivo differentiation process across a pseudotime trajectory. By linking chromatin opening to enhancer activation, we introduced the concept of “chromatin velocity” to predict lineage progression. Altogether, nano-scCUT&Tag provides unprecedented insights into the chromatin regulatory landscape of the mouse CNS.
Biography
Dr. Marek Bartosovic studied biochemistry at Comenius University in Bratislava, Slovakia, before pursuing a PhD at Masaryk University in Brno, Czech Republic, in the laboratory of Štěpánka Vanáčová. There, he investigated emerging mRNA modifications such as m^6A and the processing of non-coding RNAs.
In 2017 he joined the group of Goncalo Castelo-Branco at Karolinska Institute, where he studied the roles of epigenetics in the regulation of gene expression in the central nervous system. As part of his Marie Skłodowska-Curie Actions Seal of Excellence–funded project, he pioneered the development of single-cell CUT&Tag on the 10x Genomics platform, achieving the first single-cell histone modification profiling in the mouse brain. He further advanced the field by creating a multimodal version of nanobody-based single-cell CUT&Tag (nano-CT), capable of profiling three epigenetic modalities simultaneously in single cells. In collaboration he co-developed spatial epigenome profiling technologies on the DBiT platform. In September 2022, he established his independent laboratory at the Department of Biochemistry and Biophysics, Stockholm University, and in 2023 was awarded a prestigious Swedish foundation starting grant, based on the evaluation of his ERC Starting Grant project.
Host: Louella Vasquez, NBIS (louella.vasquez@scilifelab.se)
The talk is sponsored by the NBIS course on Epigenomics Data Analysis.
A recording will also be available on the NBIS YouTube channel.
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