Category BMEN L08 High-dimensional Single-cell Cytometry Analysis of Cancer


Abstract While cancer starts as a single cell, termed cancer stem cell (CSC), the

progeny CSCs are not created equal, but exhibit a spectrum of

phenotypes of varying renewal capacity, metastatic potential, and drug

resistance (1). Understanding this cell-to-cell difference (i.e.

heterogeneity) of CSCs holds the key to both scientific and translational

cancer research and presents us the opportunity to target and

eliminate cancer at its “stem”. Unfortunately, we do not currently have

the tools necessary to dissect CSC heterogeneity due to multiple

limitations (2). First, CSCs are extremely rare, making their isolation

parallel with finding a needle in a haystack; Second, not all biomarkers

on CSC subpopulations are known; Third, there is currently no single-

cell proteomic and signaling analyses of CSCs available; Finally, CSCs

are not static, but evolve with interacting symbiotic cells. As a result, our

current view of CSCs is “pixelated” and “isolated”, keeping us far away

from the complete understanding of CSCs.

To overcome some of the limitations mentioned above, we harvested

the power of a recent technological advancement in single-cell

detection, namely cytometry by time-of-flight (CyTOF) (3). The

University of Michigan is among the first to bring this technology on

campus. Using CyTOF, I have successfully collected and then profiled

the high-dimensional cytometry data obtained from an antibody panel

that allows for simultaneous measurement of 27 markers on a single

cell at a rate of 1000 cells per second. For the first time, we were able

to directly detect breast cancer CSCs. With further antibody panel

expansion and data mining, this study will provide the first

comprehensive and high-resolution map of the CSC subpopulations at

the proteomic and signaling levels. These results will unlock the

answers to central questions regarding cancer stemness, which will

change the paradigm of current practices in several aspects of cancer

medicine, including early detection, monitoring, therapeutics, and

ultimately lead to the development of preventative strategies to

suppress or even reverse the initiation of cancer.

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