title: Cellular Deconstruction: Finding Meaning in Individual Cell Variation.
abstract: The advent of single cell transcriptome analysis has permitted the discovery of cell-to-cell variation in transcriptome expression of even presumptively identical cells. We hypothesize that this variability reflects a many-to-one relation between transcriptome states and the phenotype of a cell. In this relation, the molecular ratios of the subsets of RNA are determined by the stoichiometric constraints of the cell systems, which underdetermine the transcriptome state. Furthermore, the variability is, in part, induced by the tissue context and is important for system-level function. This theory is analogous to theories of literary deconstruction, where multiple 'signifiers' work in opposition to one another to create meaning. By analogy, transcriptome phenotypes should be defined as subsets of RNAs comprising selected RNA systems where the system-associated RNAs are balanced with each other to produce the associated cellular function. This idea provides a framework for understanding cellular heterogeneity in phenotypic responses to variant conditions, such as disease challenge.
authors.affiliation: Department of Systems Pharmacology and Translational Therapeutics, Program in Single Cell Biology, Perelman School of Medicine, University of Pennsylvania, 3601 Hamilton Walk, Rm 37 JM Bldg, Philadelphia, PA 19104, USA. Electronic address: eberwine@upenn.edu.
authors.forename: James
authors.initials: J
authors.lastname: Eberwine
authors.affiliation: Department of Biology, Department of Computer and Information Science, School of Arts and Sciences, Program in Single Cell Biology, University of Pennsylvania, 415 S. University Ave, Philadelphia, PA 19104, USA. Electronic address: junhyong@sas.upenn.edu.
authors.forename: Junhyong
authors.initials: J
authors.lastname: Kim
mesh_terms: D005786:Gene Expression Regulation; D006801:Humans; D010641:Phenotype; D012313:RNA / Q000096:biosynthesis*; D059010:Single-Cell Analysis; D059467:Transcriptome / Q000235:genetics*
chemical_list: D012313:RNA
keywords: biological constraints; phenotype; transcriptome