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.
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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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