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A genome wide transcriptional model of the complex response to pre-TCR signalling during thymocyte differentiation

Sahni, H; Ross, S; Barbarulo, A; Solanki, A; Lau, CI; Furmanski, A; Saldaña, JI; ... Crompton, T; + view all (2015) A genome wide transcriptional model of the complex response to pre-TCR signalling during thymocyte differentiation. Oncotarget , 6 (30) pp. 28646-28660. 10.18632/oncotarget.5796. Green open access

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Abstract

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.

Type: Article
Title: A genome wide transcriptional model of the complex response to pre-TCR signalling during thymocyte differentiation
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.18632/oncotarget.5796
Publisher version: http://dx.doi.org/10.18632/oncotarget.5796
Additional information: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: DP, Immune response, Immunity, Immunology Section, foetal thymic organ cultures, genome wide transcriptional modelling, pre-TCR, thymus
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1473514
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