Dynamics of thymus organogenesis and colonization in early human development

Alison M. Farley, Lucy X. Morris, Eric Vroegindeweij, Marianne L. G. Depreter, Harsh Vaidya, Frances H. Stenhouse, Simon R. Tomlinson, Richard A. Anderson, Tom Cupedo, Jan J. Cornelissen, C. Clare Blackburn*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The thymus is the central site of T-cell development and thus is of fundamental importance to the immune system, but little information exists regarding molecular regulation of thymus development in humans. Here we demonstrate, via spatial and temporal expression analyses, that the genetic mechanisms known to regulate mouse thymus organogenesis are conserved in humans. In addition, we provide molecular evidence that the human thymic epithelium derives solely from the third pharyngeal pouch, as in the mouse, in contrast to previous suggestions. Finally, we define the timing of onset of hematopoietic cell colonization and epithelial cell differentiation in the human thymic primordium, showing, unexpectedly, that the first colonizing hematopoietic cells are CD45(+)CD34(int/-). Collectively, our data provide essential information for translation of principles established in the mouse to the human, and are of particular relevance to development of improved strategies for enhancing immune reconstitution in patients.

Original languageEnglish
Pages (from-to)2015-2026
Number of pages12
JournalDevelopment
Volume140
Issue number9
DOIs
Publication statusPublished - 1 May 2013

Keywords

  • Thymus development
  • MOUSE THYMUS
  • EPITHELIAL-CELL DIFFERENTIATION
  • Human
  • PROGENITOR CELLS
  • HUMAN-FETUS
  • LINEAGE COMMITMENT
  • GENE
  • Hematopoietic
  • Colonization
  • DELTA-LIKE 4
  • Epithelium
  • EXPRESSION
  • Mesenchyme
  • STEM-CELLS
  • T-CELL

Cite this