T2D Transcription Factor Activity

Li et al. 2025 profiled transcription-factor activity in T2D PBMC single-cell data using DoRothEA regulons and VIPER activity scoring.

Method

Li et al. 2025 used DoRothEA human regulons with confidence levels A, B, and C.
Li et al. 2025 used VIPER to calculate transcription-factor activity scores, which were stored in the Seurat object as a dorothea assay.
Li et al. 2025 identified 126 active transcription factors across T2D subtypes.

Li et al. 2025 report subtype A showed active transcription factors in central memory CD8+ T cells, memory CD8+ T cells, cytotoxic CD8+ T cells, and gamma-delta T cells.
Li et al. 2025 report HNF4A was uniquely active in naive CD4+ and naive CD8+ T cells in subtype A.
Li et al. 2025 report EPAS1 was active in memory CD8+ T cells, cytotoxic CD8+ T cells, and gamma-delta T cells in subtype A.
Li et al. 2025 report subtype B showed NFKB1 activity in regulatory CD4+ T cells and SMAD4 activity across several T-cell types.
Li et al. 2025 report subtype C showed high activity for SPI1, STAT4, SMAD1, BCL11A, IKZF1, LYL1, REST, and TBX21 in central memory CD8+ T cells.
Li et al. 2025 highlight BCL11A, BHLHE22, KLF6, and TBX21 as relevant to subtype C T-cell differentiation and immune activation.

Li et al. 2025 discuss NF-kB and STAT3 as inflammatory pathway regulators that are upregulated in T2D.
Li et al. 2025 discuss PAX6 and FOXO1 as insulin-signaling or insulin-secretion-associated transcription factors that may be downregulated in T2D.
These TF patterns provide mechanistic hypotheses connecting immune activation, metabolic dysregulation, and subtype-specific T-cell states.

This concept can support mechanistic discussion of how T2D PBMC states may be regulated at the transcriptional level.
Use cautiously: the paper reports computational TF activity inference, not direct perturbation or causal validation.

tags	concept, type-2-diabetes, pbmc, immunology, transcriptomics
aliases	T2D Transcription Factor Activity