Asymmetric binomial statistics explains organelle partitioning variance in cancer cell proliferation

Abstract

Asymmetric inheritance of organelles and compounds between daughter cells is considered a hallmark for differentiation and rejuvenation in stem-like and cancer cells, as much as a mechanism for enhancing resistance in bacteria populations. In non-differentiating homogeneous cancer cells, asymmetric division is still poorly investigated. Here, we present a method based on the binomial partitioning process that allows the measurement of asymmetric organelle partitioning with multiple live cell markers without genetically mutating the cells. We demonstrate our method by measuring simultaneously the partitioning of three cellular elements, i.e., cytoplasm, membrane, and mitochondria in human Jurkat T-cells. We found that although cell cytoplasm is partitioned symmetrically, mitochondria and membrane lipids are asymmetrically partitioned between daughter cells. Moreover, we observe that mitochondria and membrane lipids present a stable positive correlation with cytoplasm, incompatibly with a binomial partition mechanism produced by two independent partitioning processes. Our experimental apparatus, combined with our theoretical framework, could be generalized to different cell kinds, providing a tool for understanding partitioning-driven biological processes.

Emerging experimental observation suggests that asymmetrical partitioning in cell division plays an important role in cell-to-cell variability, cell fate determination, cellular aging, and rejuvenation. Here, the authors propose a method based on multicolor flow cytometry to measure asymmetric division of cellular organelles, finding that cell cytoplasm is divided symmetrically but mitochondria and membrane lipids are asymmetrically distributed, and explain these observations through a minimal model of asymmetric partitioning based on biased binomial statistics.