Transcription factor fluctuations underlie cell-to-cell variability in a signaling pathway response

Author:

Ramu Avinash12,Cohen Barak A12

Affiliation:

1. The Edison Family Center for Genome Sciences and Systems Biology, School of Medicine, Washington University in St. Louis , Saint Louis, MO 63110 , USA

2. Department of Genetics, School of Medicine, Washington University in St. Louis , Saint Louis, MO 63110 , USA

Abstract

Abstract Stochastic differences among clonal cells can initiate cell fate decisions in development or cause cell-to-cell differences in the responses to drugs or extracellular ligands. One hypothesis is that some of this phenotypic variability is caused by stochastic fluctuations in the activities of transcription factors (TFs). We tested this hypothesis in NIH3T3-CG cells using the response to Hedgehog signaling as a model cellular response. Here, we present evidence for the existence of distinct fast- and slow-responding substates in NIH3T3-CG cells. These two substates have distinct expression profiles, and fluctuations in the Prrx1 TF underlie some of the differences in expression and responsiveness between fast and slow cells. Our results show that fluctuations in TFs can contribute to cell-to-cell differences in Hedgehog signaling.

Funder

National Institute of General Medical Sciences

Publisher

Oxford University Press (OUP)

Subject

Genetics

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