Research Paper Volume 16, Issue 20 pp 13117—13131

Single-cell sequencing technology to characterize stem T-cell subpopulations in acute T-lymphoblastic leukemia and the role of stem T-cells in the disease process

Yan Li1, , Zhenwei Jia1, , Xiaoyan Liu1, , Hongbo Zhao1, , Guirong Cui1, , Jianmin Luo2, , Xiaoyang Kong1, ,

  • 1 Department of Hematology, Handan First Hospital, Handan, Hebei 056001, China
  • 2 Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China

Received: March 1, 2024       Accepted: July 17, 2024       Published: October 17, 2024      

https://doi.org/10.18632/aging.206123
How to Cite

Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Precursor T-cell acute lymphoblastic leukemia (Pre-T ALL) is a malignant neoplastic disease in which T-cells proliferate in the bone marrow. Single-cell sequencing technology could identify characteristic cell types, facilitating the study of the therapeutic mechanisms in Pre-T ALL.

Methods: The single-cell sequencing data (scRNA-seq) of Pre-T ALL were obtained from public databases. Key immune cell subpopulations involved in the progression of Pre-T ALL were identified by clustering and annotating the cellular data using AUCell. Next, pseudo-temporal analysis was performed to identify the differentiation trajectories of immune cell subpopulations using Monocle. Copy number mutation landscape of cell subpopulations was characterized by inferCNV. Finally, cellphoneDB was used to analyze intercellular communication relationships.

Results: A total of 10 cellular subpopulations were classified, with Pre-T ALL showing a higher proportion of NK/T cells. NK/T cells were further clustered into two subpopulations. Stem T cells showed a high expression of marker genes related to hematopoietic stem cells, Naive T cells had a high expression of CCR7, CCR7, RCAN3, and NK cells high-expressed KLRD1, TRDC. The cell proliferation was reduced and the activation of T cell was increased during the differentiation of stem T cells to Naive T cells. We observed interaction between stem T cells with dendritic cells such as CD74-COPA, CD74-MIF as well as co-inhibition-related interactions such as LGALS9-HAVCR2, TGFB1-TGFBR3.

Conclusion: Stem T cells were involved in the development of Pre-T-ALL through the regulatory effects of transcription factors (TFs) KLF2 and FOS and multiple ligand-receptor pairs.

Abbreviations

Pre-T-ALL: Pre-T acute lymphoblastic leukemia; scRNA-seq: Single-cell transcriptome sequencing; PCA: Principal component analysis; UMAP: Uniform Manifold Approximation and Projection; GEO: Gene Expression Omnibus; NK: Natural killer; DC: Dendritic cell; PBMMC: Peripheral blood mononuclear cell.