Identification of Plet-1 as a specific marker of early thymic epithelial progenitor cells

Abstract

The thymus is essential for a functional immune system, because the thymic stroma uniquely supports T lymphocyte development. We have previously identified the epithelial progenitor population from which the thymus arises and demonstrated its ability to generate an organized functional thymus upon transplantation. These thymic epithelial progenitor cells (TEPC) are defined by surface determinants recognized by the mAbs MTS20 and MTS24, which were also recently shown to identify keratinocyte progenitor cells in the skin. However, the biochemical nature of the MTS20 and MTS24 determinants has remained unknown. Here we show, via expression profiling of fetal mouse TEPC and their differentiated progeny and subsequent analyses, that both MTS20 and MTS24 specifically bind an orphan protein of unknown function, Placenta-expressed transcript (Plet)-1. In the postgastrulation embryo, Plet-1 expression is highly restricted to the developing pharyngeal endoderm and mesonephros until day 11.5 of embryogenesis, consistent with the MTS20 and MTS24 staining pattern; both MTS20 and MTS24 specifically bind cell lines transfected with Plet-1; and antibodies to Plet-1 recapitulate MTS20/24 staining. In adult tissues, we demonstrate expression in a number of sites, including mammary and prostate epithelia and in the pancreas, where Plet-1 is specifically expressed by the major duct epithelium, providing a specific cell surface marker for this putative reservoir of pancreatic progenitor/stem cells. Plet-1 will thus provide an invaluable tool for genetic analysis of the lineage relationships and molecular mechanisms operating in the development, homeostasis, and injury in several organ/tissue systems. thymus development ͉ MTS24 ͉ endoderm ͉ mesonephros

BTN1A1, the Mammary Gland Butyrophilin, and BTN2A2 Are Both Inhibitors of T Cell Activation

“…TECs are unique in that they are highly heterogeneous and, unlike other epithelial cells, are arranged in a three-dimensional network. Several studies have shown that mammary and thymic epithelia express various markers in common (37,38). It is interesting to note that BTN1A1 and BTN2A2 were expressed on TECs at the junction of the cortex and medulla, which is the site where T cell precursors enter the thymus via blood vessels (39).…”

Generation of Thymic Epithelial Cell Progenitors by Mouse Embryonic Stem Cells

“…2A), suggesting that cells with the phenotypes of TEPs [20][21][22] can be generated from mESCs. To determine whether the EpCAM1 þ cells express TEP-associated genes [40,41], EpCAM1 þ and EpCAM1 À cells were purified from the cultures (more than 95% purity) and subjected to real-time quantitative RT-PCR analysis for the expression of Pax1, Pax9, FoxN1, and Plet1. As shown in Figure 2B, although the expression levels of these genes in the mESC-derived EpCAM1 þ cells were lower than those in EpCAM1 þ cells purified from embryonic day (E)-12 thymi, they were significantly higher than those in the mESC-derived EpCAM1 À cells, further indicating that the mESC-derived EpCAM1 þ cells contained TEPs.…”

The Skin: A Home to Multiple Classes of Epithelial Progenitor Cells

“…A distinct compartment of the HF residing below the infundibulum and above the bulge region was identified by the presence of the MTS24 surface marker (Figure 1) (25). The gene recognized by MTS24 has now been identified as Plet-1, which encodes a protein of unknown function and may be a marker of progenitor cells in multiple tissues (26). Interestingly, MTS24 + HF cells purified by flow cytometry were highly clonogenic in vitro and exhibited a transcript profile similar to bulge stem cells suggesting that these cells may represent a progenitor cell population in the HF potentially derived from the bulge (25).…”