Thymic iNKT single cell analyses unmask the common developmental program of mouse innate T cells
| Autor: | Laurent Gapin, Tonya Brunetti, Mary Jessamine Michaels-Foster, Liyen Loh, James P. Scott-Browne, S. Harsha Krovi, Jingjing Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Science T-Lymphocytes Cell General Physics and Astronomy Systems analysis Thymus Gland Biology General Biochemistry Genetics and Molecular Biology Article Mucosal-Associated Invariant T Cells 03 medical and health sciences 0302 clinical medicine Immunity medicine Animals Cells Cultured Zinc finger transcription factor Mice Knockout Multidisciplinary Thymocytes Effector Sequence Analysis RNA Lymphopoiesis Gene Expression Profiling Signal transducing adaptor protein RNA Cell Differentiation General Chemistry Immunity Innate Cell biology DNA-Binding Proteins Mice Inbred C57BL Gene regulation in immune cells NKT cells 030104 developmental biology medicine.anatomical_structure Natural Killer T-Cells Single-Cell Analysis Homeostasis Function (biology) 030215 immunology |
| Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-15 (2020) |
| ISSN: | 2041-1723 |
| Popis: | 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. Innate-like T cells such as invariant natural killer T (iNKT) and mucosal-associated invariant T (MAIT) cells both develop in the thymus. Here the authors use single-cell RNA sequencing to show that mouse iNKT and MAIT share components of developmental regulation, with a transcription factor, Hivep3, implicated for the maturation of both cell types. |
| Databáze: | OpenAIRE |
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