title: Variation is function: Are single cell differences functionally important?: Testing the hypothesis that single cell variation is required for aggregate function.
abstract: There is a growing appreciation of the extent of transcriptome variation across individual cells of the same cell type. While expression variation may be a byproduct of, for example, dynamic or homeostatic processes, here we consider whether single-cell molecular variation per se might be crucial for population-level function. Under this hypothesis, molecular variation indicates a diversity of hidden functional capacities within an ensemble of identical cells, and this functional diversity facilitates collective behavior that would be inaccessible to a homogenous population. In reviewing this topic, we explore possible functions that might be carried by a heterogeneous ensemble of cells; however, this question has proven difficult to test, both because methods to manipulate molecular variation are limited and because it is complicated to define, and measure, population-level function. We consider several possible methods to further pursue the hypothesis that variation is function through the use of comparative analysis and novel experimental techniques.
authors.affiliation: Genomics and Computational Biology Graduate Group, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Hannah
authors.initials: H
authors.lastname: Dueck
authors.affiliation: Genomics and Computational Biology Graduate Group, University of Pennsylvania, Philadelphia, PA, USA.|Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA.|Penn Program in Single Cell Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Eberwine
authors.affiliation: Genomics and Computational Biology Graduate Group, University of Pennsylvania, Philadelphia, PA, USA.|Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA.|Penn Program in Single Cell Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Department of Biology, University of Pennsylvania, Philadelphia, PA, USA.|Department of Computer and Information Science, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Junhyong
authors.initials: J
authors.lastname: Kim
mesh_terms: D000818:Animals; D014644:Genetic Variation / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D059467:Transcriptome / Q000235:genetics* / Q000502:physiology*
keywords: bet-hedging; evolution of variation; fractional response; functional variation; single cell transcriptome; single cell variation