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

Author

Listed:
  • 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
    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))

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.

Suggested Citation

  • 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 & You J, 2020. "Single-cell RNA sequencing identifies shared differentiation paths of mouse thymic innate T cells," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18155-8
    DOI: 10.1038/s41467-020-18155-8
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    Cited by:

    1. Sang Mun Han & Eun Seo Park & Jeu Park & Hahn Nahmgoong & Yoon Ha Choi & Jiyoung Oh & Kyung Min Yim & Won Taek Lee & Yun Kyung Lee & Yong Geun Jeon & Kyung Cheul Shin & Jin Young Huh & Sung Hee Choi &, 2023. "Unique adipose tissue invariant natural killer T cell subpopulations control adipocyte turnover in mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Dong-il Kwon & Eun Seo Park & Mingyu Kim & Yoon Ha Choi & Myeong-seok Lee & Si-hyung Joo & Yeon-Woo Kang & Minji Lee & Saet-byeol Jo & Seung-Woo Lee & Jong Kyoung Kim & You Jeong Lee, 2022. "Homeostatic serum IgE is secreted by plasma cells in the thymus and enhances mast cell survival," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Guillem Sanchez Sanchez & Maria Papadopoulou & Abdulkader Azouz & Yohannes Tafesse & Archita Mishra & Jerry K. Y. Chan & Yiping Fan & Isoline Verdebout & Silvana Porco & Frédérick Libert & Florent Gin, 2022. "Identification of distinct functional thymic programming of fetal and pediatric human γδ thymocytes via single-cell analysis," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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