Abstract
Long-term video-based tracking of single A549 lung cancer cells exposed to three different concentrations of the marine toxin yessotoxin (YTX) reveals significant variation in cytotoxicity, and it confirms the potential genotoxic effects of this toxin. Tracking of single cells subject to various toxic exposure, constitutes a conceptually simple approach to elucidate lineage correlations and sub-populations which are masked in cell bulk analyses. The toxic exposure can here be considered as probing a cell population for properties and change which may include long-term adaptation to treatments. Ranking of pedigree trees according to a measure of “size,” provides definition of sub-populations. Following single cells through generations indicates that signaling cascades and experience of mother cells can pass to their descendants. Epigenetic factors and signaling downstream lineages may enhance differences between cells and partly explain observed heterogeneity in a population. Signaling downstream lineages can potentially link a variety of observations of cells making resulting data more suitable for computerized treatment. YTX exposure of A549 cells tends to cause two main visually distinguishable classes of cell death modalities (“apoptotic-like” and “necrotic-like”) with approximately equal frequency. This special property of YTX enables estimation of correlation between cell death modalities for sister cells indicating impact downstream lineages. Hence, cellular responses and adaptation to treatments might be better described in terms of effects on pedigree trees rather than considering cells as independent entities.
Highlights
Live cell time-lapse microscopy can be a valuable tool for early diagnosis in cancer therapy
Continuous single-cell tracking over many cell divisions is essential to discover rare cell populations and heterogeneous cell responses, which can be missed in cell bulk assays
The main intention of the present work is to contribute to the development of such tools via a case study of tracking individual A549 lung cancer cells exposed to the small molecule compound yessotoxin (YTX)
Summary
Live cell time-lapse microscopy can be a valuable tool for early diagnosis in cancer therapy. Continuous single-cell tracking over many cell divisions is essential to discover rare cell populations and heterogeneous cell responses, which can be missed in cell bulk assays. The main intention of the present work is to contribute to the development of such tools via a case study of tracking individual A549 lung cancer cells exposed to the small molecule compound yessotoxin (YTX). This toxin can induce different cell death modalities in many cellular systems [3, 4].
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