Project 2 | Spatial mapping of gene expression to decipher the thymic cellular crosstalk controlling central immune tolerance

Collaboration with Magali Irla, Ciml and Denis Puthier, TAGC

The thymus plays a critical role in the immune system through its unique ability to support T-cell development. This organ is composed of a large diversity of cell types (i.e. distinct stromal cells and developing T cells) that reciprocally control their respective differentiation, a process referred to as thymic crosstalk. The main objective of this PhD project is to determine in situ the impact of normal and pathological T cells on the transcriptional programs governing the stromal cell heterogeneity. Recent transcriptomic tools allow to spatially resolve genome-wide gene expression in individual tissue sections at a subcompartment or near single-cell levels. In contrast to single-cell RNA-seq, these cutting-edge technologies conserve the footprint of the tissue structure in which the occurring cellular crosstalk dictates cell fates. We will interrogate both single cell and spatial transcriptomic data as well as highly resolved imaging data sets to generate a comprehensive model of the complex cellular interplay between stromal cells and developing T cells.

Study of thymicell interactions (A) by local characterisation of transcrits genes (B)

Our objectives are (i) to provide the first spatially resolved comprehensive picture of thymus transcriptome, (ii) to spatially map the transcriptional response to thymic crosstalk perturbations and (iii) to develop computational models of cellular crosstalk and the associated bioinformatics tools. By implementing dedicated spatiofunctional graphical rendering, this project is expected to reveal the dynamically regulated transcriptional signatures by crosstalk in specific thymic niches.