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.
Highlights
The thymus is a primary lymphoid organ populated by several distinct epithelial and mesodermal cell lineages, including two thymic epithelial cell (TEC) subsets, cortical keratin 8 (K8)-positive TEC and medullary keratin 5 (K5)-positive TEC, bone marrow-derived dendritic cells and macrophages, and endothelial cells
Expression of Meis1 in the thymic microenvironment To understand the function of Meis1 in TEC differentiation, we first examined its expression in the thymus
Immunohistochemical analysis using an anti-Meis1 antibody revealed that Meis1+ cells were predominantly localized in the medulla and were very rare in the cortex, as defined by colocalized staining with K5 and keratin 14 (K14), markers for medullary keratin (K5)-positive TEC (mTEC), and by K8 and CD205, cortical keratin (K8)-positive TEC (cTEC) markers (Figure 1A)
Summary
The thymus is a primary lymphoid organ populated by several distinct epithelial and mesodermal cell lineages, including two thymic epithelial cell (TEC) subsets, cortical keratin 8 (K8)-positive TEC (cTEC) and medullary keratin 5 (K5)-positive TEC (mTEC), bone marrow-derived dendritic cells and macrophages, and endothelial cells. All of these cell types are required for proper intrathymic T cell proliferation, differentiation and selection [1,2]. P63 is of particular interest because this factor, especially one of its isoforms, DNp63, has been demonstrated to be selectively expressed in TEC stem/progenitor cells and required for their proliferation potential [15,16]
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