Identification of Plet-1 as a specific marker of early thymic epithelial progenitor cells.
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.
Depreter
Marianne G L
MG
Medical Research Council/Juvenile Diabetes Research Foundation Centre Development in Stem Cell Biology, Institute for Stem Cell Research and Centre for Regenerative Medicine, University of Edinburgh, King's Buildings, Edinburgh, United Kingdom.
Blair
Natalie F
NF
Gaskell
Terri L
TL
Nowell
Craig S
CS
Davern
Kathleen
K
Pagliocca
Adelina
A
Stenhouse
Frances H
FH
Farley
Alison M
AM
Fraser
Adrian
A
Vrana
Jan
J
Robertson
Kevin
K
Morahan
Grant
G
Tomlinson
Simon R
SR
Blackburn
C Clare
CC
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology; D015415:Biomarkers; D002460:Cell Line; D004622:Embryo, Mammalian / Q000196:embryology / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D010183:Pancreatic Ducts / Q000378:metabolism; D011257:Pregnancy Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D013234:Stem Cells / Q000276:immunology* / Q000378:metabolism*; D013950:Thymus Gland / Q000196:embryology* / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors
D000954:Antigens, Surface; D015415:Biomarkers; D008562:Membrane Glycoproteins; C514060:Mts24 protein, mouse; C526396:PLET1 protein, human; C526395:Plet-1 protein, mouse; D011257:Pregnancy Proteins; D012333:RNA, Messenger