Single-cell morphological and transcriptome analysis unveil inhibitors of polyploid giant breast cancer cells in vitro

Abstract

Considerable evidence suggests that breast cancer therapeutic resistance and relapse can be driven by polyploid giant cancer cells (PGCCs). The number of PGCCs increases with the stages of disease and therapeutic stress. Given the importance of PGCCs, it remains challenging to eradicate them. To discover effective anti-PGCC compounds, there is an unmet need to rapidly distinguish compounds that kill non-PGCCs, PGCCs, or both. Here, we establish a single-cell morphological analysis pipeline with a high throughput and great precision to characterize dynamics of individual cells. In this manner, we screen a library to identify promising compounds that inhibit all cancer cells or only PGCCs (e.g., regulators of HDAC, proteasome, and ferroptosis). Additionally, we perform scRNA-Seq to reveal altered cell cycle, metabolism, and ferroptosis sensitivity in breast PGCCs. The combination of single-cell morphological and molecular investigation reveals promising anti-PGCC strategies for breast cancer treatment and other malignancies.

Deep learning unlocks label-free viability assessment of cancer spheroids in microfluidics

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Polyploid giant cancer cells: origin, possible pathways of formation, characteristics, and mechanisms of regulation

“…This necessitates further exploration of the epigenetic reprogramming mechanisms underlying PGCC dormancy. Zhou et al proposed a single-cell morphological analysis pipeline for accurate quantification of PGCC populations and identified a selective PGCC inhibitor, Thiostrepton, along with three types of compounds capable of killing PGCCs: ferroptosis inducers, HDAC inhibitors, and proteasome inhibitors ( Zhou et al, 2023 ). This single-cell morphological study approach enables the exploration of effective anti-PGCC treatments across a wide range of malignancies, enhancing the development of the PGCC field.…”