Dynamic spatio-temporal contribution of single β5t+ cortical epithelial precursors to the thymus medulla

Eur J Immunol. 2016 Apr;46(4):846-56. doi: 10.1002/eji.201545995. Epub 2016 Jan 18.

Abstract

Intrathymic T-cell development is critically dependent on cortical and medullary thymic epithelial cells (TECs). Both epithelial subsets originate during early thymus organogenesis from progenitor cells that express the thymoproteasome subunit β5t, a typical feature of cortical TECs. Using in vivo lineage fate mapping, we demonstrate in mice that β5t(+) TEC progenitors give rise to the medullary TEC compartment early in life but significantly limit their contribution once the medulla has completely formed. Lineage-tracing studies at single cell resolution demonstrate for young mice that the postnatal medulla is expanded from individual β5t(+) cortical progenitors located at the cortico-medullary junction. These results therefore not only define a developmental window during which the expansion of medulla is efficiently enabled by progenitors resident in the thymic cortex, but also reveal the spatio-temporal dynamics that control the growth of the thymic medulla.

Keywords: Development; Epithelial cell; Medulla; Thymic progenitor cell; β5t.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Lineage / immunology
  • Cell Proliferation
  • Doxycycline / pharmacology
  • Epithelial Cells / cytology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Organogenesis / physiology
  • Proteasome Endopeptidase Complex / metabolism*
  • Stem Cells / cytology
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • Thymus Gland / cytology*
  • Thymus Gland / embryology*

Substances

  • Proteasome Endopeptidase Complex
  • proteasome subunit beta5t, mouse
  • Doxycycline