Single-cell RNA sequencing identifies shared differentiation paths of mouse thymic innate T cells

Minji Lee, Eunmin Lee, Seong Kyu Han, Yoon Ha Choi, Dong-il Kwon, Hyobeen Choi, Kwanghwan Lee, Eun Seo Park, Min-Seok Rha, Dong Jin Joo, Eui-Cheol Shin, Sanguk Kim (), Jong Kyoung Kim () and You Jeong Lee ()
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Minji Lee: Pohang University of Science and Technology (POSTECH)
Eunmin Lee: DGIST
Seong Kyu Han: Pohang University of Science and Technology (POSTECH)
Yoon Ha Choi: DGIST
Dong-il Kwon: Pohang University of Science and Technology (POSTECH)
Hyobeen Choi: Pohang University of Science and Technology (POSTECH)
Kwanghwan Lee: Pohang University of Science and Technology (POSTECH)
Eun Seo Park: DGIST
Min-Seok Rha: Graduate School of Medical Science and Engineering, KAIST
Dong Jin Joo: Yonsei University, College of Medicine
Eui-Cheol Shin: Graduate School of Medical Science and Engineering, KAIST
Sanguk Kim: Pohang University of Science and Technology (POSTECH)
Jong Kyoung Kim: DGIST
You Jeong Lee: Pohang University of Science and Technology (POSTECH)

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: Abstract Invariant natural killer T (iNKT), mucosal-associated invariant T (MAIT), and γδ T cells are innate T cells that acquire memory phenotype in the thymus and share similar biological characteristics. However, how their effector differentiation is developmentally regulated is still unclear. Here, we identify analogous effector subsets of these three innate T cell types in the thymus that share transcriptional profiles. Using single-cell RNA sequencing, we show that iNKT, MAIT and γδ T cells mature via shared, branched differentiation rather than linear maturation or TCR-mediated instruction. Simultaneous TCR clonotyping analysis reveals that thymic maturation of all three types is accompanied by clonal selection and expansion. Analyses of mice deficient of TBET, GATA3 or RORγt and additional in vivo experiments corroborate the predicted differentiation paths, while human innate T cells from liver samples display similar features. Collectively, our data indicate that innate T cells share effector differentiation processes in the thymus.

Date: 2020
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DOI: 10.1038/s41467-020-18155-8

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