RT Journal Article
SR Electronic
T1 Reinvestigation of Classic T Cell Subsets and Identification of Novel Cell Subpopulations by Single-Cell RNA Sequencing
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 396
OP 406
DO 10.4049/jimmunol.2100581
VO 208
IS 2
A1 Wang, Xuefei
A1 Shen, Xiangru
A1 Chen, Shan
A1 Liu, Hongyi
A1 Hong, Ni
A1 Zhong, Hanbing
A1 Chen, Xi
A1 Jin, Wenfei
YR 2022
UL http://www.jimmunol.org/content/208/2/396.abstract
AB Naive T cell showed the highest similarity to its scCPop counterpart in T cell subsets.Cell population identified by scRNA-seq is more homogeneous than classic T subset.ISAGhi T were identified by scRNA-seq, which may contribute to quick immune response.Classic T cell subsets are defined by a small set of cell surface markers, while single-cell RNA sequencing (scRNA-seq) clusters cells using genome-wide gene expression profiles. The relationship between scRNA-seq clustered populations (scCPops) and cell surface marker–defined classic T cell subsets remains unclear. In this article, we integrated six bead-enriched T cell subsets with 62,235 single-cell transcriptomes from human PBMCs and clustered them into nine scCPops. Bead-enriched CD4+/CD45RA+/CD25− naive T and CD8+/CD45RA+ naive T cells were mainly clustered into their scCPop counterparts, while cells from the other T cell subsets were assigned to multiple scCPops, including mucosal-associated invariant T cells and NKT cells. The multiple T cell subsets forming one scCPop exhibit similar expression patterns, but not vice versa, indicating scCPop is a more homogeneous cell population with similar cell states. Interestingly, we discovered and named IFN signaling–associated gene (ISAG) high T (ISAGhi T) cells, a T cell subpopulation that highly expressed ISAGs. We further enriched ISAGhi T cells from human PBMCs by FACS of BST2 for scRNA-seq analyses. The ISAGhi T cell cluster disappeared on t-distributed stochastic neighbor embedding plot after removing ISAGs, whereas the ISAGhi T cell cluster showed up by analysis of ISAGs alone, indicating ISAGs are the major contributor of the ISAGhi T cell cluster. BST2+ and BST2− T cells showing different efficiencies of T cell activation indicate that a high level of ISAGs may contribute to quick immune responses.