Tracking global gene expression responses in T cell differentiation

• We analyzed the global transcriptional response during T cell differentiation.
• The global response of Th17 subtype was the most different from the other subtypes.
• The response of Th0, used as control, was highly similar to that of Th1, Th2 and Treg.
• 8 major groups of differentially expressed genes were revealed for both Th0 and Th17.
• Our data suggest that Th0 is a differentiated state and, thus, may not be used as control.

Upon receiving antigens from the innate immune cells, CD4+ T cells differentiate into distinct effector cells. To probe the global responses of distinct effector cells, we analyzed transcriptome-wide expressions of Th1, Th2, Treg and Th17 using Pearson correlation, entropy and principal component analyses, with Th0 as a control. Although the global response of Th0 was quite distinct from Th17, surprisingly, it was highly similar to Th1, Th2 and Treg. Moreover, 8 major temporal groups consisting of 5704 differentially expressed genes were revealed for both Th0 and Th17. Gene functional enrichment analysis showed immune responses and metabolic processes were mainly activated between Th0 and Th17, while genes related to cell cycle and replication were differentially regulated. Moreover, we found the upregulation of several novel genes for Th0 and Th17. Overall, we deduce that Th0 is globally similar to Th1, Th2 and Treg. Our results indicate that Th0 is a differentiated state and, therefore, may not be used as a control cell type.