Dynamic spatio-temporal contribution of single beta 5t+ cortical epithelial precursors to the thymus medulla

• Published in: European journal of immunology 2016-04, Vol.46 (4), p.846-856
• Main Authors: Mayer, Carlos E, uklys, Saulius, Zhanybekova, Saule, Ohigashi, Izumi, Teh, Hong-Ying, Sansom, Stephen N, Shikama-Dorn, Noriko, Hafen, Katrin, Macaulay, Iain C, Deadman, Mary E, Ponting, Chris P, Takahama, Yousuke, Hollaender, Georg A
• Format: Article
• Language: English
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201545995

Intrathymic T-cell development is critically dependent on cortical and medullary thymic epithelial cells (TECs). Both epithelial subsets originate during early thymus organogenesis from progenitor cells that express the thymoproteasome subunit beta 5t, a typical feature of cortical TECs. Using in vivo lineage fate mapping, we demonstrate in mice that beta 5t super(+) TEC progenitors give rise to the medullary TEC compartment early in life but significantly limit their contribution once the medulla has completely formed. Lineage-tracing studies at single cell resolution demonstrate for young mice that the postnatal medulla is expanded from individual beta 5t super(+) cortical progenitors located at the cortico-medullary junction. These results therefore not only define a developmental window during which the expansion of medulla is efficiently enabled by progenitors resident in the thymic cortex, but also reveal the spatio-temporal dynamics that control the growth of the thymic medulla. The thymus medulla is subject to a dramatic expansion during the first weeks of life. Using inducible TEC-specific lineage-tracing, Mayer et al. found that single beta 5t super(+) epithelial progenitor cells located at the cortico-medullary junction adopt a medullary TEC fate and actively contribute to this postnatal growth.