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

被引:71
作者
Depreter, Marianne G. L. [1 ,2 ]
Blair, Natalie F. [1 ,2 ]
Gaskell, Terri L. [1 ,2 ]
Nowell, Craig S. [1 ,2 ]
Davernt, Kathleen [4 ]
Pagliocca, Adelina [1 ,2 ]
Stenhouse, Frances H. [1 ,2 ]
Farley, Alison M. [1 ,2 ]
Fraser, Adrian [1 ,2 ]
Vrana, Jan [1 ,2 ]
Robertson, Kevin [3 ]
Morahan, Grant [4 ]
Tomlinson, Simon R. [1 ,2 ]
Blackburn, C. Clare [1 ,2 ]
机构
[1] Univ Edinburgh, MRC, Juvenile Diab Res Fdn, Ctr Dev Stem Cell Biol,Inst Stem Cell Res, Edinburgh 3H9 3JQ, Midlothian, Scotland
[2] Univ Edinburgh, Ctr Regenerat Med, Edinburgh 3H9 3JQ, Midlothian, Scotland
[3] Univ Edinburgh, Sch Med, Div Pathway Med, Edinburgh EH16 4SB, Midlothian, Scotland
[4] Western Australian Inst Med Res, ZA-6000 Port Elizabeth, South Africa
基金
英国医学研究理事会;
关键词
thymus development; MTS24; endoderm; mesonephros;
D O I
10.1073/pnas.0711170105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:961 / 966
页数:6
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