Abstract
We have shown that the Hedgehog signalling pathway regulates T-cell development in the thymus1,2. Sonic hedgehog (Shh) from thymic epithelial cells (TEC) signals to developing thymocytes to regulate their differentiation at key pre-T-cell receptor (pre-TCR) and TCR-dependent check-points1,2. Analysis of TCR-transgenic mice showed that Hh signalling reduced TCR signal strength during pre-TCR and TCR-induced differentiation2,3. We now plan to test the impact of these changes in TCR-signal strength induced by Hedgehog signalling on TCR repertoire selection, by next generation sequencing the TCRa- and TCRb-chain repertoires from facs-sorted thymocyte populations at different stages of their development.
References
- Saldaña J, Solanki A, Lau C, Sahni H, Ross S, Furmanski A, Ono M, Holländer G and Crompton T. (2016) Sonic Hedgehog regulates thymic epithelial cell differentiation. J. Autoimmunity 68, 86.
- Rowbotham NJ, Hager-Theodorides AL, Furmanski AL, Ross SE, Outram SV, Dessens JT and Crompton T. (2009) Sonic hedgehog negatively regulates pre-TCR induced differentiation by a Gli2 dependent mechanism. Blood 113, 5144
- Furmanski AL, Barbarulo A, Solanki A, Lau CI, Sahni H, Saldana JI, D’Acquisto F, Crompton T. (2015) The transcriptional activator Gli2 modulates T-cell receptor signalling through attenuation of AP-1 and NFκB activity. J Cell Sci. 128, 2085
- Best K, Oakes T, Heather JM, Shawe-Taylor J, Chain B. (2015) Computational analysis of stochastic heterogeneity in PCR amplification efficiency revealed by single molecule barcoding. Sci Rep. 5,14629.
- Thomas N, Heather J, Ndifon W, Shawe-Taylor J, Chain B. (2013) Decombinator: a tool for fast, efficient gene assignment in T-cell receptor sequences using a finite state machine. Bioinformatics. 29, 542-50.