Based on this insight, we build multi-omics imaging tools (Gandin et al, 2025) to uncover the mechanisms and tissue-level functions associated with this layer of genome regulation. Our research focuses on how high dimensional gene expression patterns are established during development and maintained in adult tissues. Combining multiplex RNA and protein imaging with genetic perturbations, we aim to decipher spatial and temporal control of cell-fates in normal and disease tissues. These insights are crucial for understanding how the epigenome keeps cell types diverse and tissues healthy throughout an animal's life.

cycleHCR imaging of 8 protein targets in hippocampal slice

3D cell-fate map of an E6.5-7.0 mouse embryo based on spatial transcriptome data across a depth of ~310 microns

Deep-tissue spatial omics

By single-cell imaging and genomics, we recently discovered that 3D genome topology, mediated by cohesin, regulates gene co-expression in single cells rather than dictates population-wide gene expression levels (Dong et al, 2024). These findings might explain mechanisms underlying genetic disorders such as Cornelia de Lange syndrome (CdLS).

Related Publications

1. Dong, P.@, Zhang, S., Gandin, V., Xie, L., Wang, L., Lemire, A.L., Li, W., Otsuna, H., Kawase, T., Lander, A.D., Chang. H.Y., Liu, Z.@ (2024) Cohesin prevents cross-domain gene co-activation. Nature Genetics, 56(8):1654-1664.

2. Gandin, V.*, Kim, J.*, Yang, L., Lian, Y., Kawase, T., Hu, A., Rokicki, K., Fleishman, G., Tillberg, P., Castrejon, A.A., Stringer, C., Preibisch, S. Liu, Z.@ (2025) Deep-tissue transcriptomics and subcellular imaging at high spatial resolution. Science, 10.1126/science.adq2084