Cell Reports
Volume 21, Issue 4, 24 October 2017, Pages 934-942
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Thymospheres Are Formed by Mesenchymal Cells with the Potential to Generate Adipocytes, but Not Epithelial Cells

https://doi.org/10.1016/j.celrep.2017.09.090Get rights and content
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Highlights

  • Thymosphere-forming cells (TSFCs) and fibroblasts share an origin and phenotype

  • TSFCs have adipocyte, but not thymic epithelial cell, differentiation capacity

  • TSFCs may be intrathymic mesenchymal stromal/stem cells of the adult thymus

Summary

Evidence suggests that a stem-cell-driven differentiation hierarchy maintains the dynamic thymic epithelial cell (TEC) network that governs T lymphocyte development. The identification of TEC stem/progenitor cells has been a major focus in the field, and several candidates with contrasting phenotypes have been described. We sought to determine the provenance and function of the only population reported to exhibit TEC stem cell properties in the adult, a Foxn1 EpCAM cell that generates so-called thymospheres. We provide evidence that the thymosphere-forming cell (TSFC) is not a TEC stem cell but can incorporate bystander TECs into thymospheres, providing an explanation for the epithelial activity ascribed to these structures. TSFCs were found to share a phenotype, transcriptional profile, and developmental origin with thymic fibroblasts and can generate adipocytes. In summary, this study redefines the nature of bipotent TEC stem/progenitor cells in the adult thymus and highlights a potentially important mesenchymal progenitor population.

Keywords

thymus
thymic epithelial cell
stem cell
progenitor
thymosphere
MSC
mesenchyme
adipocyte

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