Journal article

Thymospheres Are Formed by Mesenchymal Cells with the Potential to Generate Adipocytes, but Not Epithelial Cells

JM Sheridan, A Keown, A Policheni, SNA Roesley, N Rivlin, N Kadouri, ME Ritchie, R Jain, J Abramson, TSP Heng, DHD Gray

Cell Reports | CELL PRESS | Published : 2017

Abstract

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 ac..

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Grants

Awarded by National Health and Medical Research Council


Funding Acknowledgements

We gratefully acknowledge members of the Gray, Strasser, and Herold labs, Dr. S. Taoudi, Prof. J. Visvader, and Prof. A. Strasser for valuable feedback. We thank the WEHI Flow Cytometry Laboratory and Centre for Dynamic Imaging for technical assistance; B. Helbert, K. Mackwell, and C. Young for mouse genotyping; G. Siciliano, K. Humphreys, S. O'Connor, and H. Marks for animal husbandry; Dr. R Boyd for antibodies; and Drs. C. Biben and T. Thomas and Prof. W. Alexander for mice. This work was supported by NHMRC grants GNT0637353 and GNT1049724; NHMRC Career Development Fellowships 1090236 (D.H.D.G.), 1104924 (M.E.R.), and 1107188 (T.S.P.H.); MIRS and MIFRS from the University of Melbourne (R. J.); and the Cancer Council of Victoria (A.P.). This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS.