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The main focus of our study is the effect of extracellular signaling on enhancing intrinsic stochastic fluctuations. As a new source of noise, the communication between cells with fluctuating numbers of components has received little attention. We use agent-based modeling to study this contribution to noise in a system of human dendritic cells responding to viral infection.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Our results, validated by single-cell experiments, show that in the transient state cell-to-cell variability in an interferon-stimulated gene (<jats:italic>DDX58<\/jats:italic>) arises from the interplay between the spatial randomness of the cellular sources of the interferon and the temporal stochasticity of its own production. The numerical simulations give insight into the time scales on which autocrine and paracrine signaling act in a heterogeneous population of dendritic cells upon viral infection. We study the effect of different factors that influence the magnitude of the cell-to-cell-variability of the induced gene, including the cell density, multiplicity of infection, and the time scale over which the cellular sources begin producing the cytokine.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>We propose a mechanism of noise propagation through extracellular communication and establish conditions under which the mechanism is operative. The cellular stochasticity of gene induction, which we investigate, is not limited to the specific interferon-induced gene we have studied; a broad distribution of copy numbers across cells is to be expected for other interferon-stimulated genes. This can lead to functional consequences for the system-level response to a viral challenge.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-7-94","type":"journal-article","created":{"date-parts":[[2013,9,25]],"date-time":"2013-09-25T18:24:30Z","timestamp":1380133470000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Noise propagation through extracellular signaling leads to fluctuations in gene expression"],"prefix":"10.1186","volume":"7","author":[{"given":"Omar P","family":"Tabbaa","sequence":"first","affiliation":[]},{"given":"German","family":"Nudelman","sequence":"additional","affiliation":[]},{"given":"Stuart C","family":"Sealfon","sequence":"additional","affiliation":[]},{"given":"Fernand","family":"Hayot","sequence":"additional","affiliation":[]},{"given":"Ciriyam","family":"Jayaprakash","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2013,9,25]]},"reference":[{"key":"1187_CR1","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1038\/nature09232","volume":"465","author":"DG Spiller","year":"2010","unstructured":"Spiller DG, Wood CD, Rand DA, White MR: Measurement of single-cell dynamics. 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