Single-Cell RNA and TCR Profiling in LGL Leukemia
Summary
In a study involving T-cell large granular lymphocyte leukemia (T-LGLL), a bone marrow failure disease responsive to immunosuppressants, researchers analyzed CD3+ T cells from 13 patients using single-cell TCR and RNA sequencing before and after antibody drug therapy. They noticed a prevailing presence of effector memory T cells in T-LGLL. There was a marked reduction in T cell receptor (TCR) variety and a significant imbalance in genes governing cell longevity and programmed cell death. Specifically, the reduced expression of apoptosis genes in CD8+ clones rebounded after the antibody drug therapy, particularly in those who responded well. The study suggests that initial apoptosis gene expression may predict treatment outcomes, but antibody drug doesn't notably alter TCR diversity.
Research Criteria
The piece highlights research on T-cell large granular lymphocyte leukemia (T-LGLL), a type of blood disorder. This investigation seeks to discern alterations in T cell clone prevalence and genetic activity pre and post-treatment for T-LGLL through the lens of individual cell sequencing.
Fig.1 Experimental design1.
Sample Type
CD3+ T cells obtained from a cohort of T-LGLL patients.
Result—T Cell scRNA-seq in T-LGLL Patients Shows an Increase in CD8+ Effector T Cells
In an intricate exploration of T cells in T-LGLL patients, researchers meticulously constructed an atlas of approximately 500,000 CD3+ T cells sourced from 13 patients, both pre- and after antibody drug treatment, juxtaposed with data from seven healthy counterparts. This comprehensive study, delineated in Fig. 1a, unveiled a pronounced expansion of CD8+ effector T cells in T-LGLL patients. Through advanced analytical techniques, including t-SNE plots and PhenoGraph clustering, the team discerned a marked variability in CD4/CD8 compositions among participants. Notably, T-LGLL patients exhibited a heightened presence of CD8+ subsets, especially prior to antibody drug intervention. Further dissection revealed a predominant surge in effector memory T cells within these patients, corroborating the established notion of their expansive nature in this context. This study, thus, offers profound insights into the nuanced landscape of T cell phenotypes and their functional states in T-LGLL patients.
Fig.2 A T cell landscape in patients with T-LGLL1.
Result—T Cell scRNA-seq in T-LGLL Patients Shows an Increase in CD8+ Effector T Cells
The nuanced interplay between TCR (T cell receptor) usage and activation states emerges as a pivotal determinant in the multifaceted landscape of T cell phenotypes. Employing diffusion maps, the study unveils a distinct, continuous pattern of T cell activation, which is intricately connected to other cellular pathways, including terminal differentiation and proinflammatory responses. This complex dance of cellular mechanisms is not only attributed to a moderate overlap of genes but also a symphony of coordinated functionalities. A meticulous analysis reveals that TCR expression accounts for a significant 22% of the variation across T cell phenotypes, underscoring the combined influence of antigenic TCR stimulation and environmental factors. In the realm of T-LGLL, clonal expansion casts a significant shadow, imprinting distinct markers on the T cell transcriptome. The research culminates in a revelation that underscores the correlation between CTL expansion, a reduction in TCR diversity, and an escalation in T cell activation, painting a comprehensive portrait of the dynamic T cell phenotypic spectrum.
Fig.3 TCR activation and use stages shape T cell phenotypes1.
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Learn moreAt Creative Biolabs, we provide an all-inclusive array of single-cell analytical tools, including both single-cell RNA sequencing and TCR profiling. Through our RNA sequencing, we dive deep into individual cell gene expression, unveiling intricate details about cell variation and function. Our TCR profiling further sharpens our ability to pinpoint specific T-cell reactions and subsets. Leveraging advanced technology and our experienced team, we offer premier data and vital knowledge, aiding innovative research and pharmaceutical progress.
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Reference
- Gao, Shouguo, et al. "Single-cell RNA sequencing coupled to TCR profiling of large granular lymphocyte leukemia T cells." Nature Communications 13.1 (2022): 1982.
