西亚试剂：Population context determines cell-to-cell variability in e

发布时间：2025-10-01

Population context determines cell-to-cell variability in endocytosis and virus infection

Berend Snijder1,2, Raphael Sacher1,2, Pauli R?m?1, Eva-Maria Damm1, Prisca Liberali1 & Lucas Pelkmans1

1 Institute of Molecular Systems Biology, ETH Zurich (Swiss Federal Institute of Technology), Wolfgang Pauli-Strasse 16, CH-8093 Zurich, Switzerland
2 Zurich PhD Program in Molecular Life Sciences, Zurich, Switzerland
Correspondence to: Lucas Pelkmans1 Correspondence and requests for materials should be addressed to L.P.

Single-cell heterogeneity in cell populations arises from a combination of intrinsic and extrinsic factors1, 2, 3. This heterogeneity has been measured for gene transcription, phosphorylation, cell morphology and drug perturbations, and used to explain various aspects of cellular physiology4, 5, 6. In all cases, however, the causes of heterogeneity were not studied. Here we analyse, for the first time, the heterogeneous patterns of related cellular activities, namely virus infection, endocytosis and membrane lipid composition in adherent human cells. We reveal correlations with specific cellular states that are defined by the population context of a cell, and we derive probabilistic models that can explain and predict most cellular heterogeneity of these activities, solely on the basis of each cell's population context. We find that accounting for population-determined heterogeneity is essential for interpreting differences between the activity levels of cell populations. Finally, we reveal that synergy between two molecular components, focal adhesion kinase and the sphingolipid GM1, enhances the population-determined pattern of simian virus 40 (SV40) infection. Our findings provide an explanation for the origin of heterogeneity patterns of cellular activities in adherent cell populations.

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