High-sensitive spatially resolved T cell receptor sequencing with SPTCR-seq.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
16 Nov 2023
16 Nov 2023
Historique:
received:
02
11
2022
accepted:
03
11
2023
medline:
27
11
2023
pubmed:
17
11
2023
entrez:
17
11
2023
Statut:
epublish
Résumé
Spatial resolution of the T cell repertoire is essential for deciphering cancer-associated immune dysfunction. Current spatially resolved transcriptomic technologies are unable to directly annotate T cell receptors (TCR). We present spatially resolved T cell receptor sequencing (SPTCR-seq), which integrates optimized target enrichment and long-read sequencing for highly sensitive TCR sequencing. The SPTCR computational pipeline achieves yield and coverage per TCR comparable to alternative single-cell TCR technologies. Our comparison of PCR-based and SPTCR-seq methods underscores SPTCR-seq's superior ability to reconstruct the entire TCR architecture, including V, D, J regions and the complementarity-determining region 3 (CDR3). Employing SPTCR-seq, we assess local T cell diversity and clonal expansion across spatially discrete niches. Exploration of the reciprocal interaction of the tumor microenvironmental and T cells discloses the critical involvement of NK and B cells in T cell exhaustion. Integrating spatially resolved omics and TCR sequencing provides as a robust tool for exploring T cell dysfunction in cancers and beyond.
Identifiants
pubmed: 37973846
doi: 10.1038/s41467-023-43201-6
pii: 10.1038/s41467-023-43201-6
pmc: PMC10654577
doi:
Substances chimiques
Receptors, Antigen, T-Cell
0
Complementarity Determining Regions
0
Receptors, Antigen, T-Cell, alpha-beta
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7432Informations de copyright
© 2023. The Author(s).
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