POSTERS
AGBT 2026 | poster #420
Integrated 3D genome, transcriptome and proteomic assays — simultaneously observing genome architecture and transcriptional activity at single-cell resolution
PaintScape™ enabled integrated 3D genome, transcriptome, and proteomic assays to simultaneously observe genome architecture and transcriptional activity at single-cell resolution
highlights
The PaintScape system enables high‑resolution identification, characterization, and direct in situ visualization of single‑cell 3D genome architecture and spatial gene expression in single cells revealing disease state specific oncogenic function.
The novel same-cell multiomic approach on the PaintScape platform shows how disruptions in genome organization drive disease mechanisms in HER2⁺ breast cancer by linking altered chromatin topology to dysregulated expression of key oncogenic pathway genes. Distinct structure-function correlations were revealed:
Copy number variation including amplification and deletions in situ in single cells and in sub-population were identified
Focal amplifications of important oncogenes: MYC, CCND1, SNAI1 in HCC1954; MET, MYC and SNAI1 in SKBR3
Loss in CDH1 DNA copy in SKBR3
Single cell ploidy variation of whole chromosomes and sub-chromosomal regions were revealed. Higher variation found in sub-population of cells with variable chromosome ploidy in HCC1954 than in SKBR3.
ecDNA copy number, structure, nuclear locations and in situ interactions were revealed
ecDNA type amplification of MYC and CCND1 genes in HCC1954 cells; MET, MYC and SNAI1 genes in SKBR3 cells
These ecDNAs show simultaneous proximity of multi-loci interactions involving key oncogenes in individual single breast cancer cell sub-populations
Interacting hubs of MYC and CCND1 in HCC1954
Interacting hubs of MYC, STAT3 and SNAI1 in SKBR3
PaintScape revealed 3D genome structure, spatial gene expression, and same cell multiomic structure-function correlations in situ
PaintScape spatial transcriptomics identified differential expression of key breast cancer related genes CDH1, SOX9, STAT3, FOXM1 that are associated with cell state, stemness and oncogenic transcriptional reprogramming between HCC1954 and SKBR3
Same cell multiomic ability of the PaintScape system identified sub-population of cancer cells with distinct 3D genome structure and spatial RNA expression profile
PaintScape transcriptomics identified high and low FOXM1 RNA expressing cells in SKBR3
High FOXM1 expressing cells show well defined TAD structure with increased enhancer-promoter interactions
These findings establish a framework for linking spatial transcriptomic signatures to structural genomic events, with implications for understanding intratumoral heterogeneity and clonal evolution in breast cancer cell lines