POSTERS
AGBT 2026 | poster #451
In situ 3D spatial characterization of genome architecture and whole transcriptome imaging in single cells with the PaintScape™ system and CosMx® SMI on ER+ breast cancer cells
A combined approach using the PaintScape™ System and CosMx® WTX enabled in situ direct visualization of 3D genome changes and spatial gene expression in single breast cancer cells
highlights
First-ever multi-platform analysis of 3D genome and spatial transcriptomics enables unparalleled investigation into the role of genome structure in transcriptomic gene expression in ER+ MCF7 breast cancer cells compared to MCF10a normal breast cells.
The combined approach of PaintScape and CosMx reveals how disruptions in genome organization drive disease mechanisms in ER⁺ breast cancer by linking altered chromatin topology to dysregulated expression of key oncogenic pathway genes.
PaintScape revealed ecDNA copy number, structure, nuclear locations and in situ interactions:
A fraction of amplified DERE targets of Chr17q and Chr20q regions were further from Chr17 or Chr20 territory suggesting possible ecDNA nature of those amplified targets
BRIP1 gene region shows very high copy number due to ecDNA amplification in MCF7
A significant fraction of the BRIP1 ecDNA formed self-interacting hub like structure in single MCF7 cells
BRIP1 ecDNA closely interacts with amplified DEREs on Chr20q including SNAI1 oncogene
CosMx WTX identified elevated expression of ER‑driven oncogenes GATA3 and CCND1 in MCF7 cells, consistent with enhanced estrogen‑dependent luminal signaling and proliferative activity
PaintScape 3D genome data shows increased enhancer-promoter interactions and strengthen intra-TAD interactions for these genes revealing mechanism of higher expression
PaintScape system characterized and directly visualized unique ecDNA structure containing relevant oncogenes BRIP1, TBX2, MED13 in MCF7
CosMx WTX shows higher expression of these genes in MCF7 compared to MCF10a revealing functional relevance of ecDNA amplification which promotes opportunistic enhancer hijacking within ecDNA elements and promoting dysregulated expression