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

TitleIdentification of Plet-1 as a specific marker of early thymic epithelial progenitor cells.
Publication TypeJournal Article
Year of Publication2008
AuthorsDepreter MGL, Blair NF, Gaskell TL, Nowell CS, Davern K, Pagliocca A, Stenhouse FH, Farley A, Fraser A, Vrana J, Robertson K, Morahan G, Tomlinson SR, C Blackburn C
JournalProc Natl Acad Sci U S A
Date Published2008 Jan 22
KeywordsAnimals, Antigens, Surface, Biological Markers, Cell Line, Embryo, Mammalian, Epithelial Cells, Epithelium, Gene Expression Regulation, Gene Expression Regulation, Developmental, Humans, Membrane Glycoproteins, Mice, Pancreatic Ducts, Pregnancy Proteins, RNA, Messenger, Stem Cells, Thymus Gland, Time Factors

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.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID18195351
PubMed Central IDPMC2242700
Grant ListG0300058 / / Medical Research Council / United Kingdom
G0400690 / / Medical Research Council / United Kingdom