Tripartite interactions between Wnt signaling, Notch and Myb for stem/progenitor cell functions during intestinal tumorigenesis.
Identifieur interne : 003092 ( PubMed/Checkpoint ); précédent : 003091; suivant : 003093Tripartite interactions between Wnt signaling, Notch and Myb for stem/progenitor cell functions during intestinal tumorigenesis.
Auteurs : Markus Germann [Australie] ; Huiling Xu [Australie] ; Jordane Malaterre [Australie] ; Shienny Sampurno [Australie] ; Mathilde Huyghe [France] ; Dane Cheasley [Australie] ; Silvia Fre [France] ; Robert G. Ramsay [Australie]Source :
- Stem cell research [ 1876-7753 ] ; 2014.
Descripteurs français
- KwdFr :
- Adénomes (anatomopathologie), Adénomes (mortalité), Adénomes (métabolisme), Animaux, Carcinogenèse, Cellules cultivées, Cellules souches (cytologie), Cellules souches (métabolisme), Différenciation cellulaire, Estimation de Kaplan-Meier, Intestins (cytologie), Intestins (métabolisme), Organoïdes (cytologie), Organoïdes (métabolisme), Prolifération cellulaire, Protéines de tissu nerveux (métabolisme), Protéines de type Wingless (métabolisme), Protéines proto-oncogènes c-myb (métabolisme), Récepteurs Notch (génétique), Récepteurs Notch (métabolisme), Récepteurs couplés aux protéines G (génétique), Récepteurs couplés aux protéines G (métabolisme), Souris, Souris de lignée C57BL, Souris knockout, Transduction du signal.
- MESH :
- anatomopathologie : Adénomes.
- cytologie : Cellules souches, Intestins, Organoïdes.
- génétique : Récepteurs Notch, Récepteurs couplés aux protéines G.
- mortalité : Adénomes.
- métabolisme : Adénomes, Cellules souches, Intestins, Organoïdes, Protéines de tissu nerveux, Protéines de type Wingless, Protéines proto-oncogènes c-myb, Récepteurs Notch, Récepteurs couplés aux protéines G.
- Animaux, Carcinogenèse, Cellules cultivées, Différenciation cellulaire, Estimation de Kaplan-Meier, Prolifération cellulaire, Souris, Souris de lignée C57BL, Souris knockout, Transduction du signal.
English descriptors
- KwdEn :
- Adenoma (metabolism), Adenoma (mortality), Adenoma (pathology), Animals, Carcinogenesis, Cell Differentiation, Cell Proliferation, Cells, Cultured, Intestines (cytology), Intestines (metabolism), Kaplan-Meier Estimate, Mice, Mice, Inbred C57BL, Mice, Knockout, Nerve Tissue Proteins (metabolism), Organoids (cytology), Organoids (metabolism), Proto-Oncogene Proteins c-myb (metabolism), Receptors, G-Protein-Coupled (genetics), Receptors, G-Protein-Coupled (metabolism), Receptors, Notch (genetics), Receptors, Notch (metabolism), Signal Transduction, Stem Cells (cytology), Stem Cells (metabolism), Wnt Proteins (metabolism).
- MESH :
- chemical , genetics : Receptors, G-Protein-Coupled, Receptors, Notch.
- chemical , metabolism : Nerve Tissue Proteins, Proto-Oncogene Proteins c-myb, Receptors, G-Protein-Coupled, Receptors, Notch, Wnt Proteins.
- cytology : Intestines, Organoids, Stem Cells.
- metabolism : Adenoma, Intestines, Organoids, Stem Cells.
- mortality : Adenoma.
- pathology : Adenoma.
- Animals, Carcinogenesis, Cell Differentiation, Cell Proliferation, Cells, Cultured, Kaplan-Meier Estimate, Mice, Mice, Inbred C57BL, Mice, Knockout, Signal Transduction.
Abstract
Deletion studies confirm Wnt, Notch and Myb transcriptional pathway engagement in intestinal tumorigenesis. Nevertheless, their contrasting and combined roles when activated have not been elucidated. This is important as these pathways are not ablated but rather are aberrantly activated during carcinogenesis. Using ApcMin/+ mice as a source of organoids we documented their transition, on a clone-by-clone basis, to cyst-like spheres with constitutively activated Wnt pathway, increased self-renewal and growth and reduced differentiation. We then looked at this transition when Myb and/or Notch1 are activated. Activated Notch promoted cyst-like organoids. Conversely growth and propagation of cyst-like, but not normal organoids were Notch-independent. Activated Myb promoted normal, but not cyst-like organoids. Interestingly the Wnt, Notch and Myb pathways were all involved in regulating the expression of the intestinal stem cell (ISC) gene Lgr5 in organoids, while ISC gene and Notch target Olfm4 was dominantly repressed by Wnt. These findings parallel mouse intestinal adenoma formation where Notch promoted the initiation, but not growth, of Wnt-driven Olfm4-repressed colon tumors. Also Myb was essential for colon tumor initiation and collateral mouse pathologies. These data reveal the complex interplay and hierarchy of transcriptional networks that operate in ISCs and uncover a shift in pathway-dependencies during tumor initiation.
DOI: 10.1016/j.scr.2014.08.002
PubMed: 25290188
Affiliations:
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Sir Peter MacCallum Cancer Department of Oncology, University of Melbourne, Australia; Department of Pathology, The University of Melbourne, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Cancer Department of Oncology, University of Melbourne, Australia; Department of Pathology, The University of Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Malaterre, Jordane" sort="Malaterre, Jordane" uniqKey="Malaterre J" first="Jordane" last="Malaterre">Jordane Malaterre</name><affiliation wicri:level="4"><nlm:affiliation>Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Cancer Department of Oncology, University of Melbourne, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; 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Sir Peter MacCallum Cancer Department of Oncology, University of Melbourne, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Cancer Department of Oncology, University of Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Fre, Silvia" sort="Fre, Silvia" uniqKey="Fre S" first="Silvia" last="Fre">Silvia Fre</name><affiliation wicri:level="3"><nlm:affiliation>Institut Curie, Centre de Recherche, Paris 75248, Cedex 05, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Curie, Centre de Recherche, Paris 75248, Cedex 05</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Cedex 05</settlement></placeName></affiliation></author><author><name sortKey="Ramsay, Robert G" sort="Ramsay, Robert G" uniqKey="Ramsay R" first="Robert G" last="Ramsay">Robert G. Ramsay</name><affiliation wicri:level="4"><nlm:affiliation>Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Cancer Department of Oncology, University of Melbourne, Australia; Department of Pathology, The University of Melbourne, Australia. Electronic address: rob.ramsay@petermac.org.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Cancer Department of Oncology, University of Melbourne, Australia; Department of Pathology, The University of Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author></analytic><series><title level="j">Stem cell research</title><idno type="eISSN">1876-7753</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adenoma (metabolism)</term><term>Adenoma (mortality)</term><term>Adenoma (pathology)</term><term>Animals</term><term>Carcinogenesis</term><term>Cell Differentiation</term><term>Cell Proliferation</term><term>Cells, Cultured</term><term>Intestines (cytology)</term><term>Intestines (metabolism)</term><term>Kaplan-Meier Estimate</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Knockout</term><term>Nerve Tissue Proteins (metabolism)</term><term>Organoids (cytology)</term><term>Organoids (metabolism)</term><term>Proto-Oncogene Proteins c-myb (metabolism)</term><term>Receptors, G-Protein-Coupled (genetics)</term><term>Receptors, G-Protein-Coupled (metabolism)</term><term>Receptors, Notch (genetics)</term><term>Receptors, Notch (metabolism)</term><term>Signal Transduction</term><term>Stem Cells (cytology)</term><term>Stem Cells (metabolism)</term><term>Wnt Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adénomes (anatomopathologie)</term><term>Adénomes (mortalité)</term><term>Adénomes (métabolisme)</term><term>Animaux</term><term>Carcinogenèse</term><term>Cellules cultivées</term><term>Cellules souches (cytologie)</term><term>Cellules souches (métabolisme)</term><term>Différenciation cellulaire</term><term>Estimation de Kaplan-Meier</term><term>Intestins (cytologie)</term><term>Intestins (métabolisme)</term><term>Organoïdes (cytologie)</term><term>Organoïdes (métabolisme)</term><term>Prolifération cellulaire</term><term>Protéines de tissu nerveux (métabolisme)</term><term>Protéines de type Wingless (métabolisme)</term><term>Protéines proto-oncogènes c-myb (métabolisme)</term><term>Récepteurs Notch (génétique)</term><term>Récepteurs Notch (métabolisme)</term><term>Récepteurs couplés aux protéines G (génétique)</term><term>Récepteurs couplés aux protéines G (métabolisme)</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Souris knockout</term><term>Transduction du signal</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Receptors, G-Protein-Coupled</term><term>Receptors, Notch</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Nerve Tissue Proteins</term><term>Proto-Oncogene Proteins c-myb</term><term>Receptors, G-Protein-Coupled</term><term>Receptors, Notch</term><term>Wnt Proteins</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Adénomes</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Cellules souches</term><term>Intestins</term><term>Organoïdes</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Intestines</term><term>Organoids</term><term>Stem Cells</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Récepteurs Notch</term><term>Récepteurs couplés aux protéines G</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Adenoma</term><term>Intestines</term><term>Organoids</term><term>Stem Cells</term></keywords><keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Adenoma</term></keywords><keywords scheme="MESH" qualifier="mortalité" xml:lang="fr"><term>Adénomes</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Adénomes</term><term>Cellules souches</term><term>Intestins</term><term>Organoïdes</term><term>Protéines de tissu nerveux</term><term>Protéines de type Wingless</term><term>Protéines proto-oncogènes c-myb</term><term>Récepteurs Notch</term><term>Récepteurs couplés aux protéines G</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Adenoma</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Carcinogenesis</term><term>Cell Differentiation</term><term>Cell Proliferation</term><term>Cells, Cultured</term><term>Kaplan-Meier Estimate</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Knockout</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Carcinogenèse</term><term>Cellules cultivées</term><term>Différenciation cellulaire</term><term>Estimation de Kaplan-Meier</term><term>Prolifération cellulaire</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Souris knockout</term><term>Transduction du signal</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Deletion studies confirm Wnt, Notch and Myb transcriptional pathway engagement in intestinal tumorigenesis. Nevertheless, their contrasting and combined roles when activated have not been elucidated. This is important as these pathways are not ablated but rather are aberrantly activated during carcinogenesis. Using ApcMin/+ mice as a source of organoids we documented their transition, on a clone-by-clone basis, to cyst-like spheres with constitutively activated Wnt pathway, increased self-renewal and growth and reduced differentiation. We then looked at this transition when Myb and/or Notch1 are activated. Activated Notch promoted cyst-like organoids. Conversely growth and propagation of cyst-like, but not normal organoids were Notch-independent. Activated Myb promoted normal, but not cyst-like organoids. Interestingly the Wnt, Notch and Myb pathways were all involved in regulating the expression of the intestinal stem cell (ISC) gene Lgr5 in organoids, while ISC gene and Notch target Olfm4 was dominantly repressed by Wnt. These findings parallel mouse intestinal adenoma formation where Notch promoted the initiation, but not growth, of Wnt-driven Olfm4-repressed colon tumors. Also Myb was essential for colon tumor initiation and collateral mouse pathologies. These data reveal the complex interplay and hierarchy of transcriptional networks that operate in ISCs and uncover a shift in pathway-dependencies during tumor initiation.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25290188</PMID><DateCreated><Year>2014</Year><Month>12</Month><Day>03</Day></DateCreated><DateCompleted><Year>2015</Year><Month>08</Month><Day>26</Day></DateCompleted><DateRevised><Year>2016</Year><Month>05</Month><Day>18</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1876-7753</ISSN><JournalIssue CitedMedium="Internet"><Volume>13</Volume><Issue>3 Pt A</Issue><PubDate><Year>2014</Year><Month>Nov</Month></PubDate></JournalIssue><Title>Stem cell research</Title><ISOAbbreviation>Stem Cell Res</ISOAbbreviation></Journal><ArticleTitle>Tripartite interactions between Wnt signaling, Notch and Myb for stem/progenitor cell functions during intestinal tumorigenesis.</ArticleTitle><Pagination><MedlinePgn>355-66</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.scr.2014.08.002</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S1873-5061(14)00091-9</ELocationID><Abstract><AbstractText>Deletion studies confirm Wnt, Notch and Myb transcriptional pathway engagement in intestinal tumorigenesis. Nevertheless, their contrasting and combined roles when activated have not been elucidated. This is important as these pathways are not ablated but rather are aberrantly activated during carcinogenesis. Using ApcMin/+ mice as a source of organoids we documented their transition, on a clone-by-clone basis, to cyst-like spheres with constitutively activated Wnt pathway, increased self-renewal and growth and reduced differentiation. We then looked at this transition when Myb and/or Notch1 are activated. Activated Notch promoted cyst-like organoids. Conversely growth and propagation of cyst-like, but not normal organoids were Notch-independent. Activated Myb promoted normal, but not cyst-like organoids. Interestingly the Wnt, Notch and Myb pathways were all involved in regulating the expression of the intestinal stem cell (ISC) gene Lgr5 in organoids, while ISC gene and Notch target Olfm4 was dominantly repressed by Wnt. These findings parallel mouse intestinal adenoma formation where Notch promoted the initiation, but not growth, of Wnt-driven Olfm4-repressed colon tumors. Also Myb was essential for colon tumor initiation and collateral mouse pathologies. These data reveal the complex interplay and hierarchy of transcriptional networks that operate in ISCs and uncover a shift in pathway-dependencies during tumor initiation.</AbstractText><CopyrightInformation>Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Germann</LastName><ForeName>Markus</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Huiling</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Cancer Department of Oncology, University of Melbourne, Australia; Department of Pathology, The University of Melbourne, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Malaterre</LastName><ForeName>Jordane</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Cancer Department of Oncology, University of Melbourne, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sampurno</LastName><ForeName>Shienny</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Cancer Department of Oncology, University of Melbourne, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Huyghe</LastName><ForeName>Mathilde</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institut Curie, Centre de Recherche, Paris 75248, Cedex 05, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cheasley</LastName><ForeName>Dane</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Cancer Department of Oncology, University of Melbourne, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fre</LastName><ForeName>Silvia</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Institut Curie, Centre de Recherche, Paris 75248, Cedex 05, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ramsay</LastName><ForeName>Robert G</ForeName><Initials>RG</Initials><AffiliationInfo><Affiliation>Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Cancer Department of Oncology, University of Melbourne, Australia; Department of Pathology, The University of Melbourne, Australia. Electronic address: rob.ramsay@petermac.org.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>09</Month><Day>28</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Stem Cell Res</MedlineTA><NlmUniqueID>101316957</NlmUniqueID><ISSNLinking>1873-5061</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C493597">Lgr5 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009419">Nerve Tissue Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D020598">Proto-Oncogene Proteins c-myb</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D043562">Receptors, G-Protein-Coupled</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051880">Receptors, Notch</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051153">Wnt Proteins</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000236" MajorTopicYN="N">Adenoma</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D063646" MajorTopicYN="N">Carcinogenesis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002454" MajorTopicYN="N">Cell Differentiation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D049109" MajorTopicYN="N">Cell Proliferation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007422" MajorTopicYN="N">Intestines</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D053208" MajorTopicYN="N">Kaplan-Meier Estimate</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018345" MajorTopicYN="N">Mice, Knockout</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009419" MajorTopicYN="N">Nerve Tissue Proteins</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009940" MajorTopicYN="N">Organoids</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020598" MajorTopicYN="N">Proto-Oncogene Proteins c-myb</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D043562" MajorTopicYN="N">Receptors, G-Protein-Coupled</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051880" MajorTopicYN="N">Receptors, Notch</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013234" MajorTopicYN="N">Stem Cells</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051153" MajorTopicYN="N">Wnt Proteins</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2014</Year><Month>04</Month><Day>04</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2014</Year><Month>07</Month><Day>09</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2014</Year><Month>08</Month><Day>02</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2014</Year><Month>10</Month><Day>8</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2014</Year><Month>10</Month><Day>8</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2015</Year><Month>8</Month><Day>27</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">25290188</ArticleId><ArticleId IdType="pii">S1873-5061(14)00091-9</ArticleId><ArticleId IdType="doi">10.1016/j.scr.2014.08.002</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Australie</li><li>France</li></country><region><li>Victoria (État)</li><li>Île-de-France</li></region><settlement><li>Cedex 05</li><li>Melbourne</li></settlement><orgName><li>Université de Melbourne</li></orgName></list><tree><country name="Australie"><noRegion><name sortKey="Germann, Markus" sort="Germann, Markus" uniqKey="Germann M" first="Markus" last="Germann">Markus Germann</name></noRegion><name sortKey="Cheasley, Dane" sort="Cheasley, Dane" uniqKey="Cheasley D" first="Dane" last="Cheasley">Dane Cheasley</name><name sortKey="Malaterre, Jordane" sort="Malaterre, Jordane" uniqKey="Malaterre J" first="Jordane" last="Malaterre">Jordane Malaterre</name><name sortKey="Ramsay, Robert G" sort="Ramsay, Robert G" uniqKey="Ramsay R" first="Robert G" last="Ramsay">Robert G. Ramsay</name><name sortKey="Sampurno, Shienny" sort="Sampurno, Shienny" uniqKey="Sampurno S" first="Shienny" last="Sampurno">Shienny Sampurno</name><name sortKey="Xu, Huiling" sort="Xu, Huiling" uniqKey="Xu H" first="Huiling" last="Xu">Huiling Xu</name></country><country name="France"><region name="Île-de-France"><name sortKey="Huyghe, Mathilde" sort="Huyghe, Mathilde" uniqKey="Huyghe M" first="Mathilde" last="Huyghe">Mathilde Huyghe</name></region><name sortKey="Fre, Silvia" sort="Fre, Silvia" uniqKey="Fre S" first="Silvia" last="Fre">Silvia Fre</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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