title: Transcriptional noise and cellular heterogeneity in mammalian macrophages.
abstract: Transcriptional noise is known to play a crucial role in heterogeneity in bacteria and yeast. Mammalian macrophages are known to exhibit cell-to-cell variation in their responses to pathogens, but the source of this heterogeneity is not known. We have developed a detailed stochastic model of gene expression that takes into account scaling effects due to cell size and genome complexity. We report the results of applying this model to simulating gene expression variability in mammalian macrophages, demonstrating a possible molecular basis for heterogeneity in macrophage signalling responses. We note that the nature of predicted transcriptional noise in macrophages is different from that in yeast and bacteria. Some molecular interactions in yeast and bacteria are thought to have evolved to minimize the effects of the high-frequency noise observed in these species. Transcriptional noise in macrophages results in slow changes to gene expression levels and would not require the type of spike-filtering circuits observed in yeast and bacteria.
authors.affiliation: Institute for Systems Biology 1441 North 34th Street, Seattle, WA 98103-8904, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ramsey
authors.forename: A
authors.initials: A
authors.lastname: Ozinsky
authors.forename: A
authors.initials: A
authors.lastname: Clark
authors.forename: K D
authors.initials: KD
authors.lastname: Smith
authors.forename: P
authors.initials: P
authors.lastname: de Atauri
authors.forename: V
authors.initials: V
authors.lastname: Thorsson
authors.forename: D
authors.initials: D
authors.lastname: Orrell
authors.forename: H
authors.initials: H
authors.lastname: Bolouri
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D008264:Macrophages / Q000378:metabolism*; D008954:Models, Biological; D012984:Software; D013269:Stochastic Processes; D014158:Transcription, Genetic