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

5.00
Hdl Handle:
http://hdl.handle.net/10547/581590
Title:
A genome wide transcriptional model of the complex response to pre-TCR signalling during thymocyte differentiation
Authors:
Sahini, Hemant; Ross, Susan; Barbarulo, Alessandro; Solanki, Anisha; Lau, Ching-In; Furmanski, Anna L.; Saldana, Jose Ignacio; Ono, Masahiro; Hubank, Mike; Barenco, Martino; Crompton, Tessa ( 0000-0002-8973-4021 )
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.
Affiliation:
University College London
Citation:
Sahni, H., Ross, S.,Barbarulo, A., Solanki, A., Lau, C., Furmanski, A., Saldaña, J.I., Ono, M., Hubank, M., Barenco, M., Crompton, T.(2015) A genome wide transcriptional model of the complex response to pre-TCR signalling during thymocyte differentiation. Oncotarget 6 (30) pp 28646-60
Publisher:
Impact Journals
Journal:
Oncotarget
Issue Date:
20-Sep-2015
URI:
http://hdl.handle.net/10547/581590
DOI:
10.18632/oncotarget.5796
PubMed ID:
26415229
Additional Links:
http://www.ncbi.nlm.nih.gov/pubmed/26415229; http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=5796&path%5B%5D=13691
Type:
Article
Language:
en
ISSN:
1949-2553
Sponsors:
This work was funded by the Wellcome Trust, MRC, BBSRC and UCL Graduate School; HS was supported by UCL-ORS/CHRAT Studentship; AB by an Istituto Pasteur/Cenci Bolognetti Foundation fellowship; MO by BBSRC David Phillips fellowship; AF by Asthma UK fellowship; MB by MRC Methodology fellowship; and AS and TC by Great Ormond Street Hospital Children’s Charity.
Appears in Collections:
Biomedical Science

Full metadata record

DC FieldValue Language
dc.contributor.authorSahini, Hemanten
dc.contributor.authorRoss, Susanen
dc.contributor.authorBarbarulo, Alessandroen
dc.contributor.authorSolanki, Anishaen
dc.contributor.authorLau, Ching-Inen
dc.contributor.authorFurmanski, Anna L.en
dc.contributor.authorSaldana, Jose Ignacioen
dc.contributor.authorOno, Masahiroen
dc.contributor.authorHubank, Mikeen
dc.contributor.authorBarenco, Martinoen
dc.contributor.authorCrompton, Tessaen
dc.date.accessioned2015-11-03T09:15:16Zen
dc.date.available2015-11-03T09:15:16Zen
dc.date.issued2015-09-20en
dc.identifier.citationSahni, H., Ross, S.,Barbarulo, A., Solanki, A., Lau, C., Furmanski, A., Saldaña, J.I., Ono, M., Hubank, M., Barenco, M., Crompton, T.(2015) A genome wide transcriptional model of the complex response to pre-TCR signalling during thymocyte differentiation. Oncotarget 6 (30) pp 28646-60en
dc.identifier.issn1949-2553en
dc.identifier.pmid26415229en
dc.identifier.doi10.18632/oncotarget.5796en
dc.identifier.urihttp://hdl.handle.net/10547/581590en
dc.description.abstractDeveloping 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.en
dc.description.sponsorshipThis work was funded by the Wellcome Trust, MRC, BBSRC and UCL Graduate School; HS was supported by UCL-ORS/CHRAT Studentship; AB by an Istituto Pasteur/Cenci Bolognetti Foundation fellowship; MO by BBSRC David Phillips fellowship; AF by Asthma UK fellowship; MB by MRC Methodology fellowship; and AS and TC by Great Ormond Street Hospital Children’s Charity.en
dc.language.isoenen
dc.publisherImpact Journalsen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/26415229en
dc.relation.urlhttp://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=5796&path%5B%5D=13691en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectpre-TCRen
dc.subjectthymusen
dc.subjectfoetal thymic organ culturesen
dc.subjectDPen
dc.subjectgenome wide transcriptional modellingen
dc.subjectimmunologyen
dc.subjectC550 Immunologyen
dc.subjectimmune responseen
dc.subjectimmunityen
dc.titleA genome wide transcriptional model of the complex response to pre-TCR signalling during thymocyte differentiationen
dc.typeArticleen
dc.contributor.departmentUniversity College Londonen
dc.identifier.journalOncotargeten
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