A Genome-wide Regulatory Network Identifies Key Transcription Factors for Memory CD8+ T Cell Development

摘要

Memory CD8⁺ T cell development is defined by the expression of a specific set of memory signature genes (MSGs). Despite recent progress, many components of the transcriptional control of memory CD8⁺ T cell development are still unknown. To identify transcription factors (TFs) and their interactions in memory CD8⁺ T cell development, we construct a genome-wide regulatory network and apply it to identify key TFs that regulate MSGs. Most of the known TFs in memory CD8⁺ T cell development are rediscovered and about a dozen new TFs are also identified. Sox4, Bhlhe40, Bach2 and Runx2 are experimentally verified and Bach2 is further shown to promote both development and recall proliferation of memory CD8⁺ T cells through Prdm1 and Id3. Gene perturbation study identifies the mode of interactions among the TFs with Sox4 as a hub. The identified TFs and insights into their interactions should facilitate further dissection of molecular mechanisms underlying memory CD8⁺ T cell development.