Identification of Plet-1 as a specific marker of early thymic epithelial progenitor cells
Identifieur interne : 000329 ( Ncbi/Merge ); précédent : 000328; suivant : 000330Identification of Plet-1 as a specific marker of early thymic epithelial progenitor cells
Auteurs : Marianne G. L. Depreter [Royaume-Uni] ; Natalie F. Blair [Royaume-Uni] ; Terri L. Gaskell [Royaume-Uni] ; Craig S. Nowell [Royaume-Uni] ; Kathleen Davern [Australie] ; Adelina Pagliocca [Royaume-Uni] ; Frances H. Stenhouse [Royaume-Uni] ; Alison M. Farley [Royaume-Uni] ; Adrian Fraser [Royaume-Uni] ; Jan Vrana [Royaume-Uni] ; Kevin Robertson [Royaume-Uni] ; Grant Morahan [Australie] ; Simon R. Tomlinson [Royaume-Uni] ; C. Clare Blackburn [Royaume-Uni]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2008.
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,
Url:
DOI: 10.1073/pnas.0711170105
PubMed: 18195351
PubMed Central: 2242700
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Identification of Plet-1 as a specific marker of early thymic epithelial progenitor cells</title>
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<affiliation wicri:level="4"><nlm:aff id="aff1">*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, West Mains Road, Edinburgh EH9 3JQ, United Kingdom;</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>*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, West Mains Road, Edinburgh EH9 3JQ</wicri:regionArea>
<orgName type="university">Université d'Édimbourg</orgName>
<placeName><settlement type="city">Édimbourg</settlement>
<region type="country">Écosse</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Blackburn, C Clare" sort="Blackburn, C Clare" uniqKey="Blackburn C" first="C. Clare" last="Blackburn">C. Clare Blackburn</name>
<affiliation wicri:level="4"><nlm:aff id="aff1">*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, West Mains Road, Edinburgh EH9 3JQ, United Kingdom;</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>*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, West Mains Road, Edinburgh EH9 3JQ</wicri:regionArea>
<orgName type="university">Université d'Édimbourg</orgName>
<placeName><settlement type="city">Édimbourg</settlement>
<region type="country">Écosse</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title>
<idno type="ISSN">0027-8424</idno>
<idno type="eISSN">1091-6490</idno>
<imprint><date when="2008">2008</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
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<front><div type="abstract" xml:lang="en"><p>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, <italic>Plet-1</italic>
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 <italic>Plet-1</italic>
; 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. <italic>Plet-1</italic>
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.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Proc Natl Acad Sci U S A</journal-id>
<journal-id journal-id-type="hwp">pnas</journal-id>
<journal-id journal-id-type="pmc">pnas</journal-id>
<journal-id journal-id-type="publisher-id">PNAS</journal-id>
<journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title>
<issn pub-type="ppub">0027-8424</issn>
<issn pub-type="epub">1091-6490</issn>
<publisher><publisher-name>National Academy of Sciences</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">18195351</article-id>
<article-id pub-id-type="pmc">2242700</article-id>
<article-id pub-id-type="publisher-id">8967</article-id>
<article-id pub-id-type="doi">10.1073/pnas.0711170105</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Biological Sciences</subject>
<subj-group><subject>Immunology</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>Identification of Plet-1 as a specific marker of early thymic epithelial progenitor cells</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Depreter</surname>
<given-names>Marianne G. L.</given-names>
</name>
<xref ref-type="aff" rid="aff1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Blair</surname>
<given-names>Natalie F.</given-names>
</name>
<xref ref-type="aff" rid="aff1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gaskell</surname>
<given-names>Terri L.</given-names>
</name>
<xref ref-type="aff" rid="aff1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Nowell</surname>
<given-names>Craig S.</given-names>
</name>
<xref ref-type="aff" rid="aff1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Davern</surname>
<given-names>Kathleen</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>†</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pagliocca</surname>
<given-names>Adelina</given-names>
</name>
<xref ref-type="aff" rid="aff1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Stenhouse</surname>
<given-names>Frances H.</given-names>
</name>
<xref ref-type="aff" rid="aff1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Farley</surname>
<given-names>Alison M.</given-names>
</name>
<xref ref-type="aff" rid="aff1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Fraser</surname>
<given-names>Adrian</given-names>
</name>
<xref ref-type="aff" rid="aff1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Vrana</surname>
<given-names>Jan</given-names>
</name>
<xref ref-type="aff" rid="aff1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Robertson</surname>
<given-names>Kevin</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>‡</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Morahan</surname>
<given-names>Grant</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>†</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tomlinson</surname>
<given-names>Simon R.</given-names>
</name>
<xref ref-type="aff" rid="aff1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Blackburn</surname>
<given-names>C. Clare</given-names>
</name>
<xref ref-type="aff" rid="aff1">*</xref>
<xref ref-type="corresp" rid="cor1"><sup>§</sup>
</xref>
</contrib>
<aff id="aff1">*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, West Mains Road, Edinburgh EH9 3JQ, United Kingdom;</aff>
<aff id="aff2"><sup>‡</sup>
Division of Pathway Medicine, University of Edinburgh Medical School, Little France Crescent, Edinburgh EH16 4SB, United Kingdom; and</aff>
<aff id="aff3"><sup>†</sup>
Western Australian Institute for Medical Research, Perth, Western Australia 6000, Australia</aff>
</contrib-group>
<author-notes><corresp id="cor1"><sup>§</sup>
To whom correspondence should be addressed. E-mail: <email>c.blackburn@ed.ac.uk</email>
</corresp>
<fn fn-type="com"><p>Communicated by Jacques F. A. P. Miller, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia, November 27, 2007</p>
</fn>
<fn fn-type="con"><p>Author contributions: G.M., S.R.T., and C.C.B. designed research; M.G.L.D., N.F.B., T.L.G., C.S.N., K.D., A.P., F.H.S., A.M.F., A.F., J.V., and K.R. performed research; K.D. and G.M. contributed new reagents/analytic tools; M.G.L.D., N.F.B., T.L.G., C.S.N., A.F., K.R., S.R.T., and C.C.B. analyzed data; and C.C.B. wrote the paper.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><day>22</day>
<month>1</month>
<year>2008</year>
</pub-date>
<pub-date pub-type="epub"><day>14</day>
<month>1</month>
<year>2008</year>
</pub-date>
<volume>105</volume>
<issue>3</issue>
<fpage>961</fpage>
<lpage>966</lpage>
<history><date date-type="received"><day>6</day>
<month>10</month>
<year>2007</year>
</date>
</history>
<copyright-statement>© 2008 by The National Academy of Sciences of the USA</copyright-statement>
<copyright-year>2008</copyright-year>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zpq00308000961.pdf"></self-uri>
<abstract><p>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, <italic>Plet-1</italic>
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 <italic>Plet-1</italic>
; 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. <italic>Plet-1</italic>
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.</p>
</abstract>
<kwd-group><kwd>thymus development</kwd>
<kwd>MTS24</kwd>
<kwd>endoderm</kwd>
<kwd>mesonephros</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>Australie</li>
<li>Royaume-Uni</li>
</country>
<region><li>Écosse</li>
</region>
<settlement><li>Édimbourg</li>
</settlement>
<orgName><li>Université d'Édimbourg</li>
</orgName>
</list>
<tree><country name="Royaume-Uni"><region name="Écosse"><name sortKey="Depreter, Marianne G L" sort="Depreter, Marianne G L" uniqKey="Depreter M" first="Marianne G. L." last="Depreter">Marianne G. L. Depreter</name>
</region>
<name sortKey="Blackburn, C Clare" sort="Blackburn, C Clare" uniqKey="Blackburn C" first="C. Clare" last="Blackburn">C. Clare Blackburn</name>
<name sortKey="Blair, Natalie F" sort="Blair, Natalie F" uniqKey="Blair N" first="Natalie F." last="Blair">Natalie F. Blair</name>
<name sortKey="Farley, Alison M" sort="Farley, Alison M" uniqKey="Farley A" first="Alison M." last="Farley">Alison M. Farley</name>
<name sortKey="Fraser, Adrian" sort="Fraser, Adrian" uniqKey="Fraser A" first="Adrian" last="Fraser">Adrian Fraser</name>
<name sortKey="Gaskell, Terri L" sort="Gaskell, Terri L" uniqKey="Gaskell T" first="Terri L." last="Gaskell">Terri L. Gaskell</name>
<name sortKey="Nowell, Craig S" sort="Nowell, Craig S" uniqKey="Nowell C" first="Craig S." last="Nowell">Craig S. Nowell</name>
<name sortKey="Pagliocca, Adelina" sort="Pagliocca, Adelina" uniqKey="Pagliocca A" first="Adelina" last="Pagliocca">Adelina Pagliocca</name>
<name sortKey="Robertson, Kevin" sort="Robertson, Kevin" uniqKey="Robertson K" first="Kevin" last="Robertson">Kevin Robertson</name>
<name sortKey="Stenhouse, Frances H" sort="Stenhouse, Frances H" uniqKey="Stenhouse F" first="Frances H." last="Stenhouse">Frances H. Stenhouse</name>
<name sortKey="Tomlinson, Simon R" sort="Tomlinson, Simon R" uniqKey="Tomlinson S" first="Simon R." last="Tomlinson">Simon R. Tomlinson</name>
<name sortKey="Vrana, Jan" sort="Vrana, Jan" uniqKey="Vrana J" first="Jan" last="Vrana">Jan Vrana</name>
</country>
<country name="Australie"><noRegion><name sortKey="Davern, Kathleen" sort="Davern, Kathleen" uniqKey="Davern K" first="Kathleen" last="Davern">Kathleen Davern</name>
</noRegion>
<name sortKey="Morahan, Grant" sort="Morahan, Grant" uniqKey="Morahan G" first="Grant" last="Morahan">Grant Morahan</name>
</country>
</tree>
</affiliations>
</record>
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