Research Papers: Immunology:
A genome wide transcriptional model of the complex response to pre-TCR signalling during thymocyte differentiation
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Hemant Sahni1, Susan Ross1, Alessandro Barbarulo1, Anisha Solanki1, Ching-In Lau1, Anna Furmanski1, José Ignacio Saldaña1, Masahiro Ono1, Mike Hubank1, Martino Barenco1,* and Tessa Crompton1,*
1 Institute of Child Health, University College London, London WC1N 1EH, UK
* These authors are co-senior authors and contributed equally to this work
Tessa Crompton, email:
Keywords: pre-TCR, thymus, foetal thymic organ cultures, DP, genome wide transcriptional modelling, Immunology Section, Immune response, Immunity
Received: July 07, 2015 Accepted: September 08, 2015 Published: September 22, 2015
Developing thymocytes require pre-TCR signalling to differentiate from CD4-CD8- double negative to CD4+CD8+ double positive cell. Here we followed the transcriptional response to pre-TCR signalling in a synchronised population of differentiating double negative thymocytes. This time series analysis revealed a complex transcriptional response, in which thousands of genes were up and down-regulated before changes in cell surface phenotype were detected. Genome-wide measurement of RNA degradation of individual genes showed great heterogeneity in the rate of degradation between different genes. We therefore used time course expression and degradation data and a genome wide transcriptional modelling (GWTM) strategy to model the transcriptional response of genes up-regulated on pre-TCR signal transduction. This analysis revealed five major temporally distinct transcriptional activities that up regulate transcription through time, whereas down-regulation of expression occurred in three waves. Our model thus placed known regulators in a temporal perspective, and in addition identified novel candidate regulators of thymocyte differentiation.
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