Many studies over the years have shown that non-genetic mechanisms for producing cell-to-cell variation can lead to highly variable behaviors across genetically identical populations of cells. Most work to date has focused on gene expression noise as the primary source of phenotypic heterogeneity, yet other sources may also contribute. In this Commentary, we explore organelle-level heterogeneity as a potential secondary source of cellular ‘noise’ that contributes to phenotypic heterogeneity. We explore mechanisms for generating organelle heterogeneity and present evidence of functional links between organelle morphology and cellular behavior. Given the many instances in which molecular-level heterogeneity has been linked to phenotypic heterogeneity, we posit that organelle heterogeneity may similarly contribute to overall phenotypic heterogeneity and underline the importance of studying organelle heterogeneity to develop a more comprehensive understanding of phenotypic heterogeneity. Finally, we conclude with a discussion of the medical challenges associated with phenotypic heterogeneity and outline how improved methods for characterizing and controlling this heterogeneity may lead to improved therapeutic strategies and outcomes for patients.
The authors declare no competing or financial interests.
The authors acknowledge the support of a National Science Foundation (NSF) Graduate Research Fellowship (A.Y.C.), a University of California, San Francisco (UCSF) Discovery Fellowship (A.Y.C.), National Institutes of Health grant [R01 GM097017 (to W.F.M.)] and an NSF grant (1515456 to W.F.M.). Both authors are members of the NSF Center for Cellular Construction, supported by NSF grant 1548297. Deposited in PMC for release after 12 months.
- © 2017. Published by The Company of Biologists Ltd