Metformin induces the AP-1 transcription factor network in normal dermal fibroblasts.
Identifieur interne : 000283 ( Main/Exploration ); précédent : 000282; suivant : 000284Metformin induces the AP-1 transcription factor network in normal dermal fibroblasts.
Auteurs : Zoe E. Gillespie [Canada] ; Chenxuan Wang [Canada] ; Flaviu Vadan [Canada] ; Topaza Y. Yu [Canada] ; Juan Ausi [Canada] ; Anthony Kusalik [Canada] ; Christopher H. Eskiw [Canada]Source :
- Scientific reports [ 2045-2322 ] ; 2019.
Descripteurs français
- KwdFr :
- MESH :
- cytologie : Peau.
- métabolisme : Facteur de transcription AP-1, Fibroblastes, Peau.
- pharmacologie : Hypoglycémiants, Metformine.
- Cellules cultivées, Humains.
English descriptors
- KwdEn :
- MESH :
- chemical , metabolism : Transcription Factor AP-1.
- chemical , pharmacology : Hypoglycemic Agents, Metformin.
- cytology : Skin.
- metabolism : Fibroblasts, Skin.
- Cells, Cultured, Humans.
Abstract
Metformin is a widely-used treatment for type 2 diabetes and is reported to extend health and lifespan as a caloric restriction (CR) mimetic. Although the benefits of metformin are well documented, the impact of this compound on the function and organization of the genome in normal tissues is unclear. To explore this impact, primary human fibroblasts were treated in culture with metformin resulting in a significant decrease in cell proliferation without evidence of cell death. Furthermore, metformin induced repositioning of chromosomes 10 and 18 within the nuclear volume indicating altered genome organization. Transcriptome analyses from RNA sequencing datasets revealed that alteration in growth profiles and chromosome positioning occurred concomitantly with changes in gene expression profiles. We further identified that different concentrations of metformin induced different transcript profiles; however, significant enrichment in the activator protein 1 (AP-1) transcription factor network was common between the different treatments. Comparative analyses revealed that metformin induced divergent changes in the transcriptome than that of rapamycin, another proposed mimetic of CR. Promoter analysis and chromatin immunoprecipitation assays of genes that changed expression in response to metformin revealed enrichment of the transcriptional regulator forkhead box O3a (FOXO3a) in normal human fibroblasts, but not of the predicted serum response factor (SRF). Therefore, we have demonstrated that metformin has significant impacts on genome organization and function in normal human fibroblasts, different from those of rapamycin, with FOXO3a likely playing a role in this response.
DOI: 10.1038/s41598-019-41839-1
PubMed: 30926854
PubMed Central: PMC6441003
Affiliations:
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Gillespie</name><affiliation wicri:level="1"><nlm:affiliation>Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon</wicri:regionArea><wicri:noRegion>Saskatoon</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry, University of Saskatchewan, Saskatoon, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, University of Saskatchewan, Saskatoon</wicri:regionArea><wicri:noRegion>Saskatoon</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Chenxuan" sort="Wang, Chenxuan" uniqKey="Wang C" first="Chenxuan" last="Wang">Chenxuan Wang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon</wicri:regionArea><wicri:noRegion>Saskatoon</wicri:noRegion></affiliation></author><author><name sortKey="Vadan, Flaviu" sort="Vadan, Flaviu" uniqKey="Vadan F" first="Flaviu" last="Vadan">Flaviu Vadan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Computer Science, University of Saskatchewan, Saskatoon, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Computer Science, University of Saskatchewan, Saskatoon</wicri:regionArea><wicri:noRegion>Saskatoon</wicri:noRegion></affiliation></author><author><name sortKey="Yu, Topaza Y" sort="Yu, Topaza Y" uniqKey="Yu T" first="Topaza Y" last="Yu">Topaza Y. Yu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon</wicri:regionArea><wicri:noRegion>Saskatoon</wicri:noRegion></affiliation></author><author><name sortKey="Ausi, Juan" sort="Ausi, Juan" uniqKey="Ausi J" first="Juan" last="Ausi">Juan Ausi</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry and Microbiology, University of Victoria, Victoria, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry and Microbiology, University of Victoria, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Kusalik, Anthony" sort="Kusalik, Anthony" uniqKey="Kusalik A" first="Anthony" last="Kusalik">Anthony Kusalik</name><affiliation wicri:level="1"><nlm:affiliation>Department of Computer Science, University of Saskatchewan, Saskatoon, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Computer Science, University of Saskatchewan, Saskatoon</wicri:regionArea><wicri:noRegion>Saskatoon</wicri:noRegion></affiliation></author><author><name sortKey="Eskiw, Christopher H" sort="Eskiw, Christopher H" uniqKey="Eskiw C" first="Christopher H" last="Eskiw">Christopher H. Eskiw</name><affiliation wicri:level="1"><nlm:affiliation>Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon, Canada. c.eskiw@usask.ca.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon</wicri:regionArea><wicri:noRegion>Saskatoon</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry, University of Saskatchewan, Saskatoon, Canada. c.eskiw@usask.ca.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, University of Saskatchewan, Saskatoon</wicri:regionArea><wicri:noRegion>Saskatoon</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2019">2019</date><idno type="RBID">pubmed:30926854</idno><idno type="pmid">30926854</idno><idno type="doi">10.1038/s41598-019-41839-1</idno><idno type="pmc">PMC6441003</idno><idno type="wicri:Area/Main/Corpus">000312</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000312</idno><idno type="wicri:Area/Main/Curation">000312</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000312</idno><idno type="wicri:Area/Main/Exploration">000312</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Metformin induces the AP-1 transcription factor network in normal dermal fibroblasts.</title><author><name sortKey="Gillespie, Zoe E" sort="Gillespie, Zoe E" uniqKey="Gillespie Z" first="Zoe E" last="Gillespie">Zoe E. Gillespie</name><affiliation wicri:level="1"><nlm:affiliation>Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon</wicri:regionArea><wicri:noRegion>Saskatoon</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry, University of Saskatchewan, Saskatoon, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, University of Saskatchewan, Saskatoon</wicri:regionArea><wicri:noRegion>Saskatoon</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Chenxuan" sort="Wang, Chenxuan" uniqKey="Wang C" first="Chenxuan" last="Wang">Chenxuan Wang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon</wicri:regionArea><wicri:noRegion>Saskatoon</wicri:noRegion></affiliation></author><author><name sortKey="Vadan, Flaviu" sort="Vadan, Flaviu" uniqKey="Vadan F" first="Flaviu" last="Vadan">Flaviu Vadan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Computer Science, University of Saskatchewan, Saskatoon, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Computer Science, University of Saskatchewan, Saskatoon</wicri:regionArea><wicri:noRegion>Saskatoon</wicri:noRegion></affiliation></author><author><name sortKey="Yu, Topaza Y" sort="Yu, Topaza Y" uniqKey="Yu T" first="Topaza Y" last="Yu">Topaza Y. Yu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon</wicri:regionArea><wicri:noRegion>Saskatoon</wicri:noRegion></affiliation></author><author><name sortKey="Ausi, Juan" sort="Ausi, Juan" uniqKey="Ausi J" first="Juan" last="Ausi">Juan Ausi</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry and Microbiology, University of Victoria, Victoria, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry and Microbiology, University of Victoria, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Kusalik, Anthony" sort="Kusalik, Anthony" uniqKey="Kusalik A" first="Anthony" last="Kusalik">Anthony Kusalik</name><affiliation wicri:level="1"><nlm:affiliation>Department of Computer Science, University of Saskatchewan, Saskatoon, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Computer Science, University of Saskatchewan, Saskatoon</wicri:regionArea><wicri:noRegion>Saskatoon</wicri:noRegion></affiliation></author><author><name sortKey="Eskiw, Christopher H" sort="Eskiw, Christopher H" uniqKey="Eskiw C" first="Christopher H" last="Eskiw">Christopher H. Eskiw</name><affiliation wicri:level="1"><nlm:affiliation>Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon, Canada. c.eskiw@usask.ca.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon</wicri:regionArea><wicri:noRegion>Saskatoon</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry, University of Saskatchewan, Saskatoon, Canada. c.eskiw@usask.ca.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, University of Saskatchewan, Saskatoon</wicri:regionArea><wicri:noRegion>Saskatoon</wicri:noRegion></affiliation></author></analytic><series><title level="j">Scientific reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cells, Cultured (MeSH)</term><term>Fibroblasts (metabolism)</term><term>Humans (MeSH)</term><term>Hypoglycemic Agents (pharmacology)</term><term>Metformin (pharmacology)</term><term>Skin (cytology)</term><term>Skin (metabolism)</term><term>Transcription Factor AP-1 (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Cellules cultivées (MeSH)</term><term>Facteur de transcription AP-1 (métabolisme)</term><term>Fibroblastes (métabolisme)</term><term>Humains (MeSH)</term><term>Hypoglycémiants (pharmacologie)</term><term>Metformine (pharmacologie)</term><term>Peau (cytologie)</term><term>Peau (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Transcription Factor AP-1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Hypoglycemic Agents</term><term>Metformin</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Peau</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Skin</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Fibroblasts</term><term>Skin</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Facteur de transcription AP-1</term><term>Fibroblastes</term><term>Peau</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Hypoglycémiants</term><term>Metformine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cells, Cultured</term><term>Humans</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Cellules cultivées</term><term>Humains</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Metformin is a widely-used treatment for type 2 diabetes and is reported to extend health and lifespan as a caloric restriction (CR) mimetic. Although the benefits of metformin are well documented, the impact of this compound on the function and organization of the genome in normal tissues is unclear. To explore this impact, primary human fibroblasts were treated in culture with metformin resulting in a significant decrease in cell proliferation without evidence of cell death. Furthermore, metformin induced repositioning of chromosomes 10 and 18 within the nuclear volume indicating altered genome organization. Transcriptome analyses from RNA sequencing datasets revealed that alteration in growth profiles and chromosome positioning occurred concomitantly with changes in gene expression profiles. We further identified that different concentrations of metformin induced different transcript profiles; however, significant enrichment in the activator protein 1 (AP-1) transcription factor network was common between the different treatments. Comparative analyses revealed that metformin induced divergent changes in the transcriptome than that of rapamycin, another proposed mimetic of CR. Promoter analysis and chromatin immunoprecipitation assays of genes that changed expression in response to metformin revealed enrichment of the transcriptional regulator forkhead box O3a (FOXO3a) in normal human fibroblasts, but not of the predicted serum response factor (SRF). Therefore, we have demonstrated that metformin has significant impacts on genome organization and function in normal human fibroblasts, different from those of rapamycin, with FOXO3a likely playing a role in this response.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">30926854</PMID><DateCompleted><Year>2020</Year><Month>10</Month><Day>27</Day></DateCompleted><DateRevised><Year>2020</Year><Month>10</Month><Day>27</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2045-2322</ISSN><JournalIssue CitedMedium="Internet"><Volume>9</Volume><Issue>1</Issue><PubDate><Year>2019</Year><Month>03</Month><Day>29</Day></PubDate></JournalIssue><Title>Scientific reports</Title><ISOAbbreviation>Sci Rep</ISOAbbreviation></Journal><ArticleTitle>Metformin induces the AP-1 transcription factor network in normal dermal fibroblasts.</ArticleTitle><Pagination><MedlinePgn>5369</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/s41598-019-41839-1</ELocationID><Abstract><AbstractText>Metformin is a widely-used treatment for type 2 diabetes and is reported to extend health and lifespan as a caloric restriction (CR) mimetic. Although the benefits of metformin are well documented, the impact of this compound on the function and organization of the genome in normal tissues is unclear. To explore this impact, primary human fibroblasts were treated in culture with metformin resulting in a significant decrease in cell proliferation without evidence of cell death. Furthermore, metformin induced repositioning of chromosomes 10 and 18 within the nuclear volume indicating altered genome organization. Transcriptome analyses from RNA sequencing datasets revealed that alteration in growth profiles and chromosome positioning occurred concomitantly with changes in gene expression profiles. We further identified that different concentrations of metformin induced different transcript profiles; however, significant enrichment in the activator protein 1 (AP-1) transcription factor network was common between the different treatments. Comparative analyses revealed that metformin induced divergent changes in the transcriptome than that of rapamycin, another proposed mimetic of CR. Promoter analysis and chromatin immunoprecipitation assays of genes that changed expression in response to metformin revealed enrichment of the transcriptional regulator forkhead box O3a (FOXO3a) in normal human fibroblasts, but not of the predicted serum response factor (SRF). Therefore, we have demonstrated that metformin has significant impacts on genome organization and function in normal human fibroblasts, different from those of rapamycin, with FOXO3a likely playing a role in this response.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Gillespie</LastName><ForeName>Zoe E</ForeName><Initials>ZE</Initials><AffiliationInfo><Affiliation>Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biochemistry, University of Saskatchewan, Saskatoon, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Chenxuan</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vadan</LastName><ForeName>Flaviu</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Computer Science, University of Saskatchewan, Saskatoon, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yu</LastName><ForeName>Topaza Y</ForeName><Initials>TY</Initials><AffiliationInfo><Affiliation>Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ausió</LastName><ForeName>Juan</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Microbiology, University of Victoria, Victoria, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kusalik</LastName><ForeName>Anthony</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Computer Science, University of Saskatchewan, Saskatoon, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Eskiw</LastName><ForeName>Christopher H</ForeName><Initials>CH</Initials><AffiliationInfo><Affiliation>Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon, Canada. c.eskiw@usask.ca.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biochemistry, University of Saskatchewan, Saskatoon, Canada. c.eskiw@usask.ca.</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>2019</Year><Month>03</Month><Day>29</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Sci Rep</MedlineTA><NlmUniqueID>101563288</NlmUniqueID><ISSNLinking>2045-2322</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007004">Hypoglycemic Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018808">Transcription Factor AP-1</NameOfSubstance></Chemical><Chemical><RegistryNumber>9100L32L2N</RegistryNumber><NameOfSubstance UI="D008687">Metformin</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005347" MajorTopicYN="N">Fibroblasts</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007004" MajorTopicYN="N">Hypoglycemic Agents</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008687" MajorTopicYN="N">Metformin</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012867" MajorTopicYN="N">Skin</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018808" MajorTopicYN="N">Transcription Factor AP-1</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>11</Month><Day>11</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>03</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>3</Month><Day>31</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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Gillespie</name></noRegion><name sortKey="Ausi, Juan" sort="Ausi, Juan" uniqKey="Ausi J" first="Juan" last="Ausi">Juan Ausi</name><name sortKey="Eskiw, Christopher H" sort="Eskiw, Christopher H" uniqKey="Eskiw C" first="Christopher H" last="Eskiw">Christopher H. Eskiw</name><name sortKey="Eskiw, Christopher H" sort="Eskiw, Christopher H" uniqKey="Eskiw C" first="Christopher H" last="Eskiw">Christopher H. Eskiw</name><name sortKey="Gillespie, Zoe E" sort="Gillespie, Zoe E" uniqKey="Gillespie Z" first="Zoe E" last="Gillespie">Zoe E. Gillespie</name><name sortKey="Kusalik, Anthony" sort="Kusalik, Anthony" uniqKey="Kusalik A" first="Anthony" last="Kusalik">Anthony Kusalik</name><name sortKey="Vadan, Flaviu" sort="Vadan, Flaviu" uniqKey="Vadan F" first="Flaviu" last="Vadan">Flaviu Vadan</name><name sortKey="Wang, Chenxuan" sort="Wang, Chenxuan" uniqKey="Wang C" first="Chenxuan" last="Wang">Chenxuan Wang</name><name sortKey="Yu, Topaza Y" sort="Yu, Topaza Y" uniqKey="Yu T" first="Topaza Y" last="Yu">Topaza Y. Yu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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