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Thymic iNKT single cell analyses unmask the common developmental program of mouse innate T cells

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  • S. Harsha Krovi

    (University of Colorado Anschutz Medical Campus
    Evergrande Center for Immunologic diseases at Harvard Medical School and Brigham and Women’s Hospital)

  • Jingjing Zhang

    (University of Colorado Anschutz Medical Campus
    Stanford Health Care, Department of Pathology, Stanford University)

  • Mary Jessamine Michaels-Foster

    (University of Colorado Anschutz Medical Campus)

  • Tonya Brunetti

    (University of Colorado Anschutz Medical Campus)

  • Liyen Loh

    (University of Colorado Anschutz Medical Campus)

  • James Scott-Browne

    (University of Colorado Anschutz Medical Campus
    National Jewish Health)

  • Laurent Gapin

    (University of Colorado Anschutz Medical Campus
    National Jewish Health)

Abstract

Most T lymphocytes leave the thymus as naïve cells with limited functionality. However, unique populations of innate-like T cells differentiate into functionally distinct effector subsets during their development in the thymus. Here, we profiled >10,000 differentiating thymic invariant natural killer T (iNKT) cells using single-cell RNA sequencing to produce a comprehensive transcriptional landscape that highlights their maturation, function, and fate decisions at homeostasis. Our results reveal transcriptional profiles that are broadly shared between iNKT and mucosal-associated invariant T (MAIT) cells, illustrating a common core developmental program. We further unmask a mutual requirement for Hivep3, a zinc finger transcription factor and adapter protein. Hivep3 is expressed in early precursors and regulates the post-selection proliferative burst, differentiation and functions of iNKT cells. Altogether, our results highlight the common requirements for the development of innate-like T cells with a focus on how Hivep3 impacts the maturation of these lymphocytes.

Suggested Citation

  • S. Harsha Krovi & Jingjing Zhang & Mary Jessamine Michaels-Foster & Tonya Brunetti & Liyen Loh & James Scott-Browne & Laurent Gapin, 2020. "Thymic iNKT single cell analyses unmask the common developmental program of mouse innate T cells," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-20073-8
    DOI: 10.1038/s41467-020-20073-8
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    Cited by:

    1. 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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