A genome wide transcriptional model of the complex response to pre-TCR signalling during thymocyte differentiation
Article
Sahni, Hemant, Susan, Ross, Barbarulo, Alessandro, Solanki, Anisha, Lau, Ching-In, Furmanski, Anna, Saldaña, J., Ono, Masahiro, Hubank, Mike, Barenco, Martino and Crompton, Tessa 2015. A genome wide transcriptional model of the complex response to pre-TCR signalling during thymocyte differentiation. Oncotarget. 6 (30), pp. 28646-28660. https://doi.org/10.18632/oncotarget.5796
Authors | Sahni, Hemant, Susan, Ross, Barbarulo, Alessandro, Solanki, Anisha, Lau, Ching-In, Furmanski, Anna, Saldaña, J., Ono, Masahiro, Hubank, Mike, Barenco, Martino and Crompton, Tessa |
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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. |
Keywords | pre-TCR; thymus; foetal thymic organ cultures; DP; genome wide transcriptional modelling; Immunology Section; Immune response; Immunity |
Journal | Oncotarget |
Journal citation | 6 (30), pp. 28646-28660 |
ISSN | 1949-2553 |
Year | 2015 |
Publisher | Impact Journals |
Publisher's version | License CC BY |
Supplemental file | License CC BY |
Supplemental file | License CC BY |
Digital Object Identifier (DOI) | https://doi.org/10.18632/oncotarget.5796 |
Publication dates | |
22 Sep 2015 | |
Publication process dates | |
Deposited | 31 Jan 2017 |
Accepted | 08 Sep 2015 |
Funder | Wellcome Trust |
Medical Research Council (MRC) | |
Biotechnology and Biological Sciences Research Council (BBSRC) | |
UCL Graduate School | |
Wellcome Trust | |
Medical Research Council | |
Biotechnology and Biological Sciences Research Council | |
University College London | |
Asthma UK | |
Istituto Pasteur-Fondazione Cenci Bolognetti | |
Great Ormond Street Hospital for Children | |
Copyright information | © 2015 The authors. |
https://repository.uel.ac.uk/item/8548z
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Publisher's version
5796-79220-3-PB Oncotarget Vol.6 No. 3.pdf | ||
License: CC BY |
Supplemental file
oncotarget-06-28646-s001 (2).pdf | ||
License: CC BY |
SP file - tables.xlsx | ||
License: CC BY |
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