Single-cell RNA sequencing coupled to TCR profiling of large granular lymphocyte leukemia T cells

Basic information
Cell
564,270
Sample
32

Technology
10X Genomics
Omics
scRNA-seq
Source
PBMCs

Dataset ID
35411048
Platform
Illumina HiSeq 3000
Species
Human
Disease
T-LGLL,Healthy
Age range
26 - 85
Update date
2022-04-11
Summary

T-cell large granular lymphocyte leukemia (T-LGLL) is a lymphoproliferative disease and bone marrow failure syndrome which responds to immunosuppressive therapies. We show single-cell TCR coupled with RNA sequencing of CD3+ T cells from 13 patients, sampled before and after alemtuzumab treatments. Effector memory T cells and loss of T cell receptor (TCR) repertoire diversity are prevalent in T-LGLL. Shared TCRA and TCRB clonotypes are absent. Deregulation of cell survival and apoptosis gene programs, and marked downregulation of apoptosis genes in CD8+ clones, are prominent features of T-LGLL cells. Apoptosis genes are upregulated after alemtuzumab treatment, especially in responders than non-responders; baseline expression levels of apoptosis genes are predictive of hematologic response. Alemtuzumab does not attenuate TCR clonality, and TCR diversity is further skewed after treatment. Inferences made from analysis of single cell data inform understanding of the pathophysiologic mechanisms of clonal expansion and persistence in T-LGLL.

Overall design

We applied scTCR-seq coupled with scRNA-seq to CD3+ T cells obtained from a relatively large cohort of T-LGLL patients and 7 healthy donors

Contributors

Shouguo Gao†✉️, Zhijie Wu†

Contact

shouguo.gao@nih.gov (Shouguo Gao)

snRNA-Seq
Sample nameSample titleDiseaseGenderAgeSourceTreatmentTechnologyPlatformOmicsSample IDDataset IDAction
No data available