PLX113851

GSE147081: Single Cell RNA-Seq of CD8+ T cell subsets responding to tumor

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Tissue-resident memory CD8+ T cells (Trm) provide host protection through continuous surveillance of non-lymphoid tissues. While the relevance of Trm in diverse diseases ranging from infection to cancer is appreciated, the development and functional heterogeneity of Trm remain poorly understood. Using single-cell RNA-sequencing (scRNA-seq) and genetic reporter mice, we identified discrete lineages of intestinal antigen-specific CD8+ T cells, including a Blimp1hiId3lo tissue-resident effector cell population most prominent in the early phase of acute viral and bacterial infections, and a molecularly distinct Blimp1loId3hi tissue-resident memory population that subsequently accumulated at later infection timepoints. These distinct Trm populations where characterized by unique transcriptional programs including differential roles for transcriptional regulators Blimp1, T-bet, Id2, and Id3 in supporting and maintaining intestinal Trm heterogeneity during infection. Extending our analysis to malignant tissue, we also identified discrete populations of effector-like and memory-like CD8+ T cell populations with tissue-resident gene-expression signatures within tumors that shared features of terminally-exhausted and progenitor-exhausted T cells, respectively. Clarification of CD8+ T cell ontogeny and heterogeneity in non-lymphoid tissues holds broad implications for enhancing vaccination and immunotherapy approaches. SOURCE: Ananda Goldrath (agoldrath@ucsd.edu) - Goldrath Lab UCSD