Genetic modulation during thymocyte development an integrative approach based on microarray meta-analysis

The thymus is a primary lymphoid organ where T cell development takes place. The alpha-beta T lymphocyte lineage has well defined developmental stages, wherein the T cell receptor (TCR) structure and interaction ability are tested so that to guarantee central tolerance in the immune system. We conducted a meta-analysis using microarray data of T cell precursors (thymocytes) but only experiments where the thymocytes were isolated based on the developmental stages defined by the expression of CD4 and CD8 markers. Our approach allowed us to isolate meaningfully different gene categories regardless of the microarray platform, and to provide a perspective on gene modulation during this process. After filtering the data, the remaining 991 genes were sorted according to their expression profile across 27 comparisons, resulting in 15 clusters. We coupled the cluster expression profiles with the evidence in the literature, providing a comprehensive view of thymocyte development. As expected, our results associate the gene expression with TCR signaling pathways. Additionally, they revealed new genes associated with this process, and provided more evidence to understand the role of genes already known to be important to T cell development. Lastly, the clusters were related with other surface receptor signaling pathways, as well as chemotaxis and cell migration process, highlighting the importance of external stimuli to thymocyte differentiation. In conclusion, we have identified, through data integration, pathways and molecules that should have relevant impact on T cell development. We believe that the meta-analysis reported herein improved the comprehension on how the gene expression is organized temporally, providing a global perspective on the thymocyte gene modulation waves.