Single-cell RNA sequencing sheds new light on cancer cells' varied response to chemotherapy

Sept. 3, 2020

Chemotherapy works by attacking rapidly dividing cells within the body. But small pockets of cancer cells can withstand its assault, allowing the cancer eventually to return. Gaining a better understanding of why some cancer cells survive while others die is critical for making chemotherapy more effective, according to a press release and Jun Hee Lee, PhD, a cancer researcher at the University of Michigan Rogel Cancer Center.

Using a technique called single-cell RNA sequencing, a research team from U-M was able to show for the first time how individual cells within a single population of cancer cells respond differently to the DNA damage caused by chemotherapy. The responses, they found, fall into three groups: activating genes that control cell death, cell division, or stress response, according to findings published in Cell Reports.

"Collectively, we observed that cells with different fates actually had completely distinct sets of activated genes and that these different 'transcriptomic landscapes' dictate the fates of cells after DNA damage from chemotherapy," says Lee, co-senior author of the study and an associate professor of molecular and integrative physiology at Michigan Medicine.

While DNA contains the complete instruction manual for the cell, sequences that are transcribed into RNA tell the story of which genes are switched on or off at a given time—that is, which sets of individual instructions are being acted upon. The transcriptome is the complete set of these RNA sequences within a given cell.

The study analyzed more than 10,000 cells from three colon cancer cell lines. The cells were exposed to the chemotherapy agent fluorouracil, which is commonly used against colon cancer and other types of cancer. Some of the observations were replicated with additional techniques and different chemotherapy drugs.

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