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Microfluidic system-based time-course tracking of physical proximity between cells and its effect on gene expression for elucidating live single cancer-immune cell interactions

By Bianca C.T Flores, Smriti Chawla, Ning Ma, Chad Sanada, Praveen Kumar Kujur, Ludimilla T.D Chinen, Kyle Hukari, Mark Lynch, Naveen Ramalingam, Debarka Sengupta, Stefanie S Jeffrey

Posted 14 Nov 2021
bioRxiv DOI: 10.1101/2021.11.13.468447

Cell-cell communication and physical interactions play a vital role in cancer initiation, homeostasis, progression, and immune response. Here, we report a system that combines live capture of different cell types, co-incubation, time-lapse imaging, and gene expression profiling of doublets using a microfluidic integrated fluidic circuit (IFC) that enables measurement of physical distances between cells and the associated transcriptional profiles due to cell-cell interactions. The temporal variations in natural killer (NK) - triple-negative breast cancer (TNBC) cell distances were tracked and compared with terminally profiled cellular transcriptomes. The results showed the time-bound activities of regulatory modules and alluded to the existence of transcriptional memory. Our experimental and bioinformatic approaches serve as a proof of concept for interrogating live cell interactions at doublet resolution, which can be applied across different cancers and cell types.

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