Thymospheres Are Formed by Mesenchymal Cells with the Potential to Generate Adipocytes, but Not Epithelial Cells
Julie M. Sheridan,
Ashleigh Keown,
Antonia Policheni,
Siti N.A. Roesley,
Noa Rivlin,
Noam Kadouri,
Matthew E. Ritchie,
Reema Jain,
Jakub Abramson,
Tracy S.P. Heng,
Daniel H.D. Gray
Affiliations
Julie M. Sheridan
Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC, Australia
Ashleigh Keown
Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
Antonia Policheni
Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC, Australia
Siti N.A. Roesley
Monash Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia
Noa Rivlin
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel
Noam Kadouri
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel
Matthew E. Ritchie
Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC, Australia
Reema Jain
Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC, Australia
Jakub Abramson
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel
Tracy S.P. Heng
Monash Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia
Daniel H.D. Gray
Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC, Australia; Corresponding author
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. : The phenotype of putative bipotent epithelial stem/progenitor cells in the adult thymus has been controversial. Sheridan et al. find that a prominent candidate, the FoxN1−EpCAM− sphere-forming cell, harbors no epithelial stem/progenitor capacity and present evidence that they are a unique intrathymic mesenchymal stromal/stem cell population with adipocyte differentiation capacity. Keywords: thymus, thymic epithelial cell, stem cell, progenitor, thymosphere, MSC, mesenchyme, adipocyte
