Informal Seminar - Professor Taro Kitazawa
Memory defines who we are. Converging studies propose that memories are allocated to a sparse ensemble of neurons that are activated during learning and reactivated during recall. However, only a limited fraction of learning-activated neurons is reactivated, and the cellular and molecular mechanisms that determine reactiva-tion propensity remain unknown.
In the first half of this seminar, I will focus on memory allocation during learning and present our single-cell (sc) multi-omics approach. After aversive memory formation, we collected the amygdala, medial prefrontal cortex, and dorsal hippocampus and performed 10x Genomics scMultiome (RNA and ATAC) together with multimodal nanobody-scCUT&Tag (nanoCT; ATAC plus H3K27ac, H3K27me3, and FOS). By focusing on the epigenetic memory of neuronal activation, we identified learning-specific gene regulatory modules distinct from baseline activity, outlining regulatory programs by which neurons discriminate learning-relevant stimuli (manuscript in preparation).
In the second half, I will introduce HisTrac-seq, a whole-genome history-tracing platform we developed to overcome the snapshot limitation of conventional single-cell sequencing. HisTrac-seq enzymatically labels adenines in genomic DNA to record past gene regulatory states, enabling "time machine"-like temporal multi-omics that links past and present molecular profiles within the same cells. We extended HisTrac-seq to single cells and, in a neurodifferentiation dataset, discovered unexpected abrupt cell identity transitions ("identity jumps") associated with alterations in signaling and epigenetic states (Kawamura et al., bioRxiv 2025).
Finally, I will introduce our ongoing scHisTrac-seq study of memory, which links learning-induced molecular states to recall-time reactivation. This enables a direct comparison of reactivated versus non-reactivated neu-rons to uncover the epigenetic and transcriptional basis of ensemble reactivation - a core feature of the memory engram definition.
Reference -
Whole-genome single-cell multimodal history tracing to reveal cell identity transition. Kawamura, KY., Khalil, V., Kitazawa, T. bioRxiv 2025 (https://doi.org/10.1101/2025.08.12.669973)
Biography -
Taro Kitazawa is a Group Leader at the Danish Research Institute of Translational Neuroscience (DANDRITE; Nordic-EMBL Partnership) and Associate Professor at Aarhus University in Denmark. He earned his PhD from the University of Tokyo in 2014. He then trained at the Friedrich Miescher Institute for Biomedical Research (FMI, Switzerland), where his work helped uncover how a bipartite Polycomb chromatin signature controls stimulus–response transcription of immediate early genes during neuronal maturation (Kitazawa et al., Nature
Genetics, 2021). In Denmark, his lab pursues neurogenomics of both memory and neurodevelopment, inte-grating biological discovery with technology development. This includes whole-genome history tracing to link past and present regulatory states in the same single-cells, exemplified by HisTrac-seq (Kawamura et al., bioRxiv 2025; under revision).
Selected funding & recognitions: ERC Starting Grant (2021), FENS–Kavli Network of Excellence (FKNE) Scholar (2023–2027), JST PRESTO Sakigake Researcher (from 2024).
Hosted by Micheal Elowitz