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Article Dans Une Revue EMBO Journal Année : 2022

Single‐cell transcriptomics uncovers an instructive T‐cell receptor role in adult γδ T‐cell lineage commitment

Résumé

After entering the adult thymus, bipotent T-cell progenitors give rise to ab or cd T cells. To determine whether the cd T-cell receptor (TCR) has an instructive role in cd T-cell lineage commitment or only "confirms" a pre-established cd Τ-cell lineage state, we exploited mice lacking expression of LAT, an adaptor required for cd TCR signaling. Although these mice showed a T-cell development block at the CD4 À CD8 À double-negative third (DN3) stage, 0.3% of their DN3 cells expressed intermediate levels of cd TCR (further referred to as cd int) at their surface. Single-cell transcriptomics of LAT-deficient DN3 cd int cells demonstrated no sign of commitment to the cd T-cell lineage, apart from cd TCR expression. Although the lack of LAT is thought to tightly block DN3 cell development, we unexpectedly found that 25% of LAT-deficient DN3 cd int cells were actively proliferating and progressed up to the DN4 stage. However, even those cells failed to turn on the transcriptional program associated with the cd T-cell lineage. Therefore, the cd TCR-LAT signaling axis builds upon a cd T-cell uncommitted lineage state to fully instruct adult cd T-cell lineage specification.
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hal-03763565 , version 1 (29-08-2022)

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Sara Scaramuzzino, Delphine Potier, Robin Ordioni, Pierre Grenot, Dominique Payet‐bornet, et al.. Single‐cell transcriptomics uncovers an instructive T‐cell receptor role in adult γδ T‐cell lineage commitment. EMBO Journal, 2022, 41, ⟨10.15252/embj.2021110023⟩. ⟨hal-03763565⟩
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