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

Nat Commun. 2020 Dec 7;11(1):6238. doi: 10.1038/s41467-020-20073-8.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism
  • Gene Expression Profiling / methods
  • Immunity, Innate / genetics
  • Immunity, Innate / immunology*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mucosal-Associated Invariant T Cells / cytology
  • Mucosal-Associated Invariant T Cells / immunology
  • Mucosal-Associated Invariant T Cells / metabolism
  • Natural Killer T-Cells / cytology
  • Natural Killer T-Cells / immunology*
  • Natural Killer T-Cells / metabolism
  • Sequence Analysis, RNA / methods
  • Single-Cell Analysis / methods*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Thymocytes / cytology
  • Thymocytes / immunology
  • Thymocytes / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / immunology*
  • Thymus Gland / metabolism


  • DNA-Binding Proteins
  • Hivep3 protein, mouse