Pheno-seq - linking visual features and gene expression in 3D cell culture systems.

Area of Science:

• Oncology
• Genomics
• Cell Biology

Background:

• 3D cell cultures advance cancer research by mimicking tissue properties and drug responses.
• Limited understanding exists on linking morphological heterogeneity to transcriptomes in these models.

Purpose of the Study:

• Introduce pheno-seq, a method to directly correlate visual features of 3D cell cultures with their transcriptome.
• Investigate the relationship between morphology and gene expression in cancer spheroids.

Main Methods:

• Developed and applied pheno-seq to patient-derived breast and colorectal cancer (CRC) spheroids.
• Linked morphological phenotypes to transcriptomic profiles.

Main Results:

• Identified epithelial-to-mesenchymal transition signatures associated with invasive growth in breast cancer spheroids.
• Linked long-term proliferation in CRC models to a PROX1-positive cancer stem cell subtype.

Conclusions:

• Pheno-seq integrates transcriptome analysis with morphological phenotypes.
• This approach offers novel insights into the molecular origins of intratumor heterogeneity.