Profiling Dormant Cancer Cells through Mechanical and Transcriptomic Analysis

Assiut University
Mahmoud Nady Abdelmoez Atta
Cellular dormancy poses a significant challenge in cancer research. Dormant cancer cells remain undetected until they reactivate, leading to disease recurrence. The mechanical interactions between cells and the microenvironment, closely tied to their molecular states, are key in distinguishing between proliferation and dormancy. Here, we propose a high-throughput approach that combines cytometry and transcriptomics to profile the state of cancer cells under mechanical confinement. The approach involves encapsulating single cells in hydrogel beads with tailored mechanical properties, resembling the in-vivo condition of the microenvironment of the cancer cells. This confinement induces a shift in the proliferative phenotype of the cells. This enables us to identify the dormant cell population via longitudinally profiling quantities of RNA and DNA content with flow cytometry. Additionally, the approach characterizes the transcriptional state of the dormant cell population by single-cell RNA-sequencing. To understand the mechanical interactions between the cancer cells and the microenvironment, we aim to develop three mechanical force sensors. These sensors will quantify the mechanical force field in the hydrogel beads respectively by imaging, flow cytometry, and sequencing. Through this work, we aim to advance our understanding and contribute to the development of more targeted cancer therapy strategies.
