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Single-cell and spatial transcriptomics reveals memory CD8+ T cell differentiation fostered by monocytes through TGF-β signaling

ABSTRACT: Upon antigen recognition, CD8+ T cells undergo a robust expansion and differentiation to give rise to effector and memory CD8+ T cells. The spatial determinants for effector and memory CD8+ T cell fate decision during acute infection is poorly understood. By integrating single-cell RNA sequencing (scRNA-seq) and spatial resolved transcriptomics, we investigated the anatomical locations, cell-cell interactions and molecular mechanisms that contribute to memory CD8+ T cell differentiation. We found naïve CD8+ T cells adopted a divergent differentiation trajectory where they rapidly differentiated into memory precursors (MP) and IFN-responsive cells which represent the entry point of effector T cell lineage.In the spleen, monocytes were largely colocalized with CD8+ MP cells in an antigen stimulation-dependent manner. CD8+ T cells primed with monocytes, compared to DC populations, had significantly increased memory T cell differentiation. Mechanistically, monocytes promoted memory CD8+ T cell differentiation by providing TGF-β signaling. Our study reveals a novel spatial mechanism for memory CD8+ T cell fate decision, shedding lights on the importance of monocytes and TGF-β in fostering memory CD8+ T cell development.

ORGANISM(S): Mus musculus

PROVIDER: GSE266606 | GEO | 2025/06/05

REPOSITORIES: GEO

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Single-cell and spatial transcriptomics reveals memory CD8+ T cell differentiation fostered by monocytes through TGF-β signaling

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