RNA-Seq and ATAC-Seq Analyses Reveal Global Transcriptional and Chromatin Accessibility Profiling of gamma-delta T17 differentiation
We investigated the molecular mechanisms of gamma-delta T17 differentiation and their functions by sorting IL-17A+ Vgamma4, IL-17A- Vgamma4, and Vgamma1 subsets from mouse spleen and conducting RNA-seq and ATAC-seq analyses. We identified differentially expressed genes (DEGs) and differentially accessible regions (DARs) related to the function and differentiation of peripheral gamma-delta T17 cells. Using WGCNA and Metascape analysis, we identified key modules and MCODEs involved in the control of the three subsets. We also identified 26 key transcription factors enriched in three subsets, which contributed to deciphering the potential molecular mechanism driving gamma-delta T17 differentiation. Furthermore, we conducted chromatin accessibility profiling under gamma-delta T17 differentiation by ATAC-seq. The top six candidate genes were screened for gamma-delta T17 differentiation and function by integrating RNA-seq and ATAC-seq analysis, and the results were further confirmed using RT-qPCR. Finally, we performed association analysis of candidate genes with the RNA-seq database of psoriasis to elucidate the functional relationship. Our findings provide a novel insight into understanding the molecular mechanisms of gamma-delta T17 differentiation and function and may improve the development of therapeutic approaches or drugs targeting gamma-delta T17 for autoimmune diseases. The raw data have been submitted to the GEO database