Imperial College London
Portrait Picture

ProfessorBorisLenhard

Faculty of Medicine, Institute of Clinical Sciences

Professor of Computational Biology
 
 
 
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Contact

 

+44 (0)20 7594 0911b.lenhard Website

 
 
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Assistant

 

Mr Alastair Douglas Ivor Williams +44 (0)20 3313 4318

 
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Location

 

6.12CLMS BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Karimi:2021:10.1038/s41467-020-20306-w,
author = {Karimi, MM and Guo, Y and Cui, X and Pallikonda, HA and Horkova, V and Dore, MH and Wang, Y-F and Ruiz, Gil S and Rodriguez-Eteban, G and Robles, Rebollo I and Bruno, L and Georgieva, R and Patel, B and Elliott, J and Dauphars, D and Krangel, MS and Lenhard, B and Heyn, H and Fisher, AG and Stepanek, O and Merkenschlager, M},
doi = {10.1038/s41467-020-20306-w},
journal = {Nature Communications},
title = {The order and logic of CD4 CD8 lineage choice and differentiation in mouse thymus},
url = {http://dx.doi.org/10.1038/s41467-020-20306-w},
volume = {12},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - CD4 and CD8 mark helper and cytotoxic T cell lineages, respectively, and serve as coreceptors for MHC-restricted TCR recognition. How coreceptor expression is matched with TCR specificity is central to understanding CD4/CD8 lineage choice, but visualising coreceptor gene activity in individual selection intermediates has been technically challenging. It therefore remains unclear whether the sequence of coreceptor gene expression in selection intermediates follows a stereotypic pattern, or is responsive to signaling. Here we use single cell RNA sequencing (scRNA-seq) to classify mouse thymocyte selection intermediates by coreceptor gene expression. In the unperturbed thymus, Cd4+Cd8a- selection intermediates appear before Cd4-Cd8a+ selection intermediates, but the timing of these subsets is flexible according to the strength of TCR signals. Our data show that selection intermediates discriminate MHC class prior to the loss of coreceptor expression and suggest a model where signal strength informs the timing of coreceptor gene activity and ultimately CD4/CD8 lineage choice.
AU  - Karimi,MM
AU  - Guo,Y
AU  - Cui,X
AU  - Pallikonda,HA
AU  - Horkova,V
AU  - Dore,MH
AU  - Wang,Y-F
AU  - Ruiz,Gil S
AU  - Rodriguez-Eteban,G
AU  - Robles,Rebollo I
AU  - Bruno,L
AU  - Georgieva,R
AU  - Patel,B
AU  - Elliott,J
AU  - Dauphars,D
AU  - Krangel,MS
AU  - Lenhard,B
AU  - Heyn,H
AU  - Fisher,AG
AU  - Stepanek,O
AU  - Merkenschlager,M
DO  - 10.1038/s41467-020-20306-w
PY  - 2021///
SN  - 2041-1723
TI  - The order and logic of CD4 CD8 lineage choice and differentiation in mouse thymus
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-020-20306-w
UR  - http://hdl.handle.net/10044/1/85325
VL  - 12
ER  -
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