Meis1 Is Required for the Maintenance of Postnatal Thymic Epithelial Cells

Abstract

Most epithelial tissues retain stem/progenitor cells to maintain homeostasis of the adult tissues; however, the existence of a thymic epithelial cell (TEC) progenitor capable of maintaining homeostasis of the postnatal thymus remains unclear. Here, we show that a cell population expressing high levels of Meis1, a homeodomain transcription factor, is enriched in TECs with an immature cellular phenotype. These TECs selectively express genes involved in embryonic thymic organogenesis and epithelial stem cell maintenance, and also have the potential to proliferate and differentiate into mature TEC populations. Furthermore, postnatal inactivation of Meis1 in TECs caused disorganization of the thymic architecture, which ultimately leads to premature disappearance of the thymus. There was an age-associated reduction in the proportion of the TEC population expressing high levels of Meis1, which may also be related to thymic involution. These findings indicate that Meis1 is potentially involved in the maintenance of postnatal TECs with progenitor activity that is required for homeostasis of the postnatal thymus.

Meis3 is required for neural crest invasion of the gut during zebrafish enteric nervous system development

“…Several studies have highlighted the role of Meis proteins in the regulation of progenitor cell maintenance, proliferation, and differentiation during organogenesis. For example, Meis1 serves an essential role in progenitor/stem cell development in various developmental and postembryonic contexts, such as neural stem cell development ( Barber et al ., 2013 ), hematopoiesis ( Ariki et al ., 2014 ), and thymic epithelial cell progenitor maintenance ( Hirayama et al ., 2014 ). Meis2 regulates limb outgrowth ( Capdevila et al ., 1999 ), olfactory neurogenesis ( Agoston et al ., 2014 ), human cardiac development ( Paige et al ., 2012 ), and the differentiation of craniofacial cartilage in zebrafish embryos ( Melvin et al ., 2013 ).…”

Challenging the current model of early‐onset myasthenia gravis pathogenesis in the light of the MGTX trial and histological heterogeneity of thymectomy specimens

“…However, there is thymic output beyond that age . Declining levels of FOXN1 and declining proliferative activity of TECs with age contribute to involution . After age 40, the natural loss of T cells from the T cell repertoire cannot be compensated by the output from the involuting thymus but is counterbalanced by homeostatic proliferation of historic T cells.…”

“…42 Declining levels of FOXN1 [43][44][45][46] and declining proliferative activity of TECs with age contribute to involution. 47,48 After age 40, the natural loss of T cells from the T cell repertoire cannot be compensated by the output from the involuting thymus but is counterbalanced by homeostatic proliferation of historic T cells. This leads to reduced T cell repertoire diversity and more senescent T cells 49 that are more resistance to regulatory signals, generate more interferon (IFN)-␥ , and increase the risk of inflammatory reactions.…”

Generation of a Tlx1CreER‐Venus knock‐in mouse strain for the study of spleen development

“…Tamoxifen (final concentration: 10 mg/ml, Sigma-Aldrich, St Louis, MO) was prepared as described previously (Hirayama et al, 2014). In brief, 50 mg of tamoxifen was dissolved into 500 ml of ethanol at 55 C followed by addition of 4.5 ml of warmed sunflower oil and mixed thoroughly by vortexing.…”