Journal
DEVELOPMENT
Volume 140, Issue 9, Pages 2015-2026Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.087320
Keywords
Thymus development; Human; Hematopoietic; Epithelium; Mesenchyme; Colonization
Categories
Funding
- Leukaemia and Lymphoma Research
- Medical Research Council, UK
- Wellcome Trust
- EU FP7 integrated project EuroSystem
- Netherlands Organisation for Scientific Research [Zon-MW Vidi grant] [91710377]
- Medical Research Council [G1100357, G0700711B, G1002118, G1002033] Funding Source: researchfish
- MRC [G1002118, G1100357, G1002033] Funding Source: UKRI
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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.
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