Imperial College London

Professor Dame Amanda Fisher

Faculty of MedicineInstitute of Clinical Sciences

Head of the Institute of Clinical Sciences







Ms Alessandra Lisini +44 (0)20 3313 8236




CRB (Clinical Research Building)Hammersmith Campus






BibTex format

author = {Blevins, R and Bruno, L and Carroll, T and Elliott, J and Marcais, A and Loh, C and Hertweck, A and Krek, A and Rajewsky, N and Chen, C-Z and Fisher, AG and Merkenschlager, M},
doi = {10.1371/journal.pgen.1005020},
journal = {Plos Genetics},
title = {microRNAs Regulate Cell-to-Cell Variability of Endogenous Target Gene Expression in Developing Mouse Thymocytes},
url = {},
volume = {11},
year = {2015}

RIS format (EndNote, RefMan)

AB - The development and homeostasis of multicellular organisms relies on gene regulationwithin individual constituent cells. Gene regulatory circuits that increase the robustness ofgene expression frequently incorporate microRNAs as post-transcriptional regulators.Computational approaches, synthetic gene circuits and observations in model organismspredict that the co-regulation of microRNAs and their target mRNAs can reduce cell-to-cellvariability in the expression of target genes. However, whether microRNAs directly regulatevariability of endogenous gene expression remains to be tested in mammalian cells. Herewe use quantitative flow cytometry to show that microRNAs impact on cell-to-cell variabilityof protein expression in developing mouse thymocytes. We find two distinct mechanismsthat control variation in the activation-induced expression of the microRNA target CD69.First, the expression of miR-17 and miR-20a, two members of the miR-17-92 cluster, is coregulatedwith the target mRNA Cd69 to form an activation-induced incoherent feed-forwardloop. Another microRNA, miR-181a, acts at least in part upstream of the target mRNA Cd69to modulate cellular responses to activation. The ability of microRNAs to render gene expressionmore uniform across mammalian cell populations may be important for normal developmentand for disease.
AU - Blevins,R
AU - Bruno,L
AU - Carroll,T
AU - Elliott,J
AU - Marcais,A
AU - Loh,C
AU - Hertweck,A
AU - Krek,A
AU - Rajewsky,N
AU - Chen,C-Z
AU - Fisher,AG
AU - Merkenschlager,M
DO - 10.1371/journal.pgen.1005020
PY - 2015///
SN - 1553-7404
TI - microRNAs Regulate Cell-to-Cell Variability of Endogenous Target Gene Expression in Developing Mouse Thymocytes
T2 - Plos Genetics
UR -
UR -
VL - 11
ER -