Indian Hedgehog regulates senescence in bone marrow-derived mesenchymal stem cell through modulation of ROS/mTOR/4EBP1, p70S6K1/2 pathway.
Identifieur interne : 000107 ( Main/Exploration ); précédent : 000106; suivant : 000108Indian Hedgehog regulates senescence in bone marrow-derived mesenchymal stem cell through modulation of ROS/mTOR/4EBP1, p70S6K1/2 pathway.
Auteurs : Mahmoud Al-Azab [République populaire de Chine] ; Bing Wang [République populaire de Chine] ; Abdalkhalig Elkhider [République populaire de Chine] ; Williams Walana [République populaire de Chine, Ghana] ; Weiping Li [République populaire de Chine] ; Bo Yuan [République populaire de Chine] ; Yunshan Ye [République populaire de Chine] ; Yawei Tang [République populaire de Chine] ; Marwan Almoiliqy [République populaire de Chine] ; Salah Adlat [République populaire de Chine] ; Jing Wei [République populaire de Chine] ; Yan Zhang [République populaire de Chine] ; Xia Li [République populaire de Chine]Source :
- Aging [ 1945-4589 ] ; 2020.
Abstract
Premature senescence of bone marrow-derived mesenchymal stem cells (BMSC) remains a major concern for their application clinically. Hedgehog signaling has been reported to regulate aging-associated markers and MSC skewed differentiation. Indian Hedgehog (IHH) is a ligand of Hedgehog intracellular pathway considered as an inducer in chondrogenesis of human BMSC. However, the role of IHH in the aging of BMSC is still unclear. This study explored the role IHH in the senescence of BMSC obtained from human samples and senescent mice. Isolated BMSC were transfected with IHH siRNA or incubated with exogenous IHH protein and the mechanisms of aging and differentiation investigated. Moreover, the interactions between IHH, and mammalian target of rapamycin (mTOR) and reactive oxygen species (ROS) were evaluated using the corresponding inhibitors and antioxidants. BMSC transfected with IHH siRNA showed characteristics of senescence-associated features including increased senescence-associated β-galactosidase activity (SA-β-gal), induction of cell cycle inhibitors (p53/p16), development of senescence-associated secretory phenotype (SASP), activation of ROS and mTOR pathways as well as the promotion of skewed differentiation. Interestingly, BMSC treatment with IHH protein reversed the senescence markers and corrected biased differentiation. Moreover, IHH shortage-induced senescence signs were compromised after mTOR and ROS inhibition. Our findings presented anti-aging activity for IHH in BMSC through down-regulation of ROS/mTOR pathways. This discovery might contribute to increasing the therapeutic, immunomodulatory and regenerative potency of BMSC and introduce a novel remedy in the management of aging-related diseases.
DOI: 10.18632/aging.102958
PubMed: 32235006
PubMed Central: PMC7185126
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sortKey="Yuan, Bo" sort="Yuan, Bo" uniqKey="Yuan B" first="Bo" last="Yuan">Bo Yuan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning</wicri:regionArea><wicri:noRegion>Liaoning</wicri:noRegion></affiliation></author><author><name sortKey="Ye, Yunshan" sort="Ye, Yunshan" uniqKey="Ye Y" first="Yunshan" last="Ye">Yunshan Ye</name><affiliation wicri:level="1"><nlm:affiliation>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning</wicri:regionArea><wicri:noRegion>Liaoning</wicri:noRegion></affiliation></author><author><name sortKey="Tang, Yawei" sort="Tang, Yawei" uniqKey="Tang Y" first="Yawei" last="Tang">Yawei Tang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning</wicri:regionArea><wicri:noRegion>Liaoning</wicri:noRegion></affiliation></author><author><name sortKey="Almoiliqy, Marwan" sort="Almoiliqy, Marwan" uniqKey="Almoiliqy M" first="Marwan" last="Almoiliqy">Marwan Almoiliqy</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pharmacology, College of Pharmacy, Dalian Medical University, Liaoning, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pharmacology, College of Pharmacy, Dalian Medical University, Liaoning</wicri:regionArea><wicri:noRegion>Liaoning</wicri:noRegion></affiliation></author><author><name sortKey="Adlat, Salah" sort="Adlat, Salah" uniqKey="Adlat S" first="Salah" last="Adlat">Salah Adlat</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Molecular Epigenetics of MOE, School of Life Science, Northeast Normal University, Changchun, Jilin Province, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Molecular Epigenetics of MOE, School of Life Science, Northeast Normal University, Changchun, Jilin Province</wicri:regionArea><wicri:noRegion>Jilin Province</wicri:noRegion></affiliation></author><author><name sortKey="Wei, Jing" sort="Wei, Jing" uniqKey="Wei J" first="Jing" last="Wei">Jing Wei</name><affiliation wicri:level="1"><nlm:affiliation>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning</wicri:regionArea><wicri:noRegion>Liaoning</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Yan" sort="Zhang, Yan" uniqKey="Zhang Y" first="Yan" last="Zhang">Yan Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Rheumatology and Immunology, The Second Affiliated Hospital of Dalian Medical University, Liaoning, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Rheumatology and Immunology, The Second Affiliated Hospital of Dalian Medical University, Liaoning</wicri:regionArea><wicri:noRegion>Liaoning</wicri:noRegion></affiliation></author><author><name sortKey="Li, Xia" sort="Li, Xia" uniqKey="Li X" first="Xia" last="Li">Xia Li</name><affiliation wicri:level="1"><nlm:affiliation>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning</wicri:regionArea><wicri:noRegion>Liaoning</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32235006</idno><idno type="pmid">32235006</idno><idno type="doi">10.18632/aging.102958</idno><idno type="pmc">PMC7185126</idno><idno type="wicri:Area/Main/Corpus">000096</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000096</idno><idno type="wicri:Area/Main/Curation">000096</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000096</idno><idno 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University, Guangzhou, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Immunology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Wang, Bing" sort="Wang, Bing" uniqKey="Wang B" first="Bing" last="Wang">Bing Wang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning</wicri:regionArea><wicri:noRegion>Liaoning</wicri:noRegion></affiliation></author><author><name sortKey="Elkhider, Abdalkhalig" sort="Elkhider, Abdalkhalig" uniqKey="Elkhider A" first="Abdalkhalig" last="Elkhider">Abdalkhalig Elkhider</name><affiliation wicri:level="1"><nlm:affiliation>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning</wicri:regionArea><wicri:noRegion>Liaoning</wicri:noRegion></affiliation></author><author><name sortKey="Walana, Williams" sort="Walana, Williams" uniqKey="Walana W" first="Williams" last="Walana">Williams Walana</name><affiliation wicri:level="1"><nlm:affiliation>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning</wicri:regionArea><wicri:noRegion>Liaoning</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Microbiology, University for Development Studies, Tamale, Ghana.</nlm:affiliation><country xml:lang="fr">Ghana</country><wicri:regionArea>Department of Clinical Microbiology, University for Development Studies, Tamale</wicri:regionArea><wicri:noRegion>Tamale</wicri:noRegion></affiliation></author><author><name sortKey="Li, Weiping" sort="Li, Weiping" uniqKey="Li W" first="Weiping" last="Li">Weiping Li</name><affiliation wicri:level="1"><nlm:affiliation>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning</wicri:regionArea><wicri:noRegion>Liaoning</wicri:noRegion></affiliation></author><author><name sortKey="Yuan, Bo" sort="Yuan, Bo" uniqKey="Yuan B" first="Bo" last="Yuan">Bo Yuan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning</wicri:regionArea><wicri:noRegion>Liaoning</wicri:noRegion></affiliation></author><author><name sortKey="Ye, Yunshan" sort="Ye, Yunshan" uniqKey="Ye Y" first="Yunshan" last="Ye">Yunshan Ye</name><affiliation wicri:level="1"><nlm:affiliation>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning</wicri:regionArea><wicri:noRegion>Liaoning</wicri:noRegion></affiliation></author><author><name sortKey="Tang, Yawei" sort="Tang, Yawei" uniqKey="Tang Y" first="Yawei" last="Tang">Yawei Tang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning</wicri:regionArea><wicri:noRegion>Liaoning</wicri:noRegion></affiliation></author><author><name sortKey="Almoiliqy, Marwan" sort="Almoiliqy, Marwan" uniqKey="Almoiliqy M" first="Marwan" last="Almoiliqy">Marwan Almoiliqy</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pharmacology, College of Pharmacy, Dalian Medical University, Liaoning, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pharmacology, College of Pharmacy, Dalian Medical University, Liaoning</wicri:regionArea><wicri:noRegion>Liaoning</wicri:noRegion></affiliation></author><author><name sortKey="Adlat, Salah" sort="Adlat, Salah" uniqKey="Adlat S" first="Salah" last="Adlat">Salah Adlat</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Molecular Epigenetics of MOE, School of Life Science, Northeast Normal University, Changchun, Jilin Province, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Molecular Epigenetics of MOE, School of Life Science, Northeast Normal University, Changchun, Jilin Province</wicri:regionArea><wicri:noRegion>Jilin Province</wicri:noRegion></affiliation></author><author><name sortKey="Wei, Jing" sort="Wei, Jing" uniqKey="Wei J" first="Jing" last="Wei">Jing Wei</name><affiliation wicri:level="1"><nlm:affiliation>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning</wicri:regionArea><wicri:noRegion>Liaoning</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Yan" sort="Zhang, Yan" uniqKey="Zhang Y" first="Yan" last="Zhang">Yan Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Rheumatology and Immunology, The Second Affiliated Hospital of Dalian Medical University, Liaoning, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Rheumatology and Immunology, The Second Affiliated Hospital of Dalian Medical University, Liaoning</wicri:regionArea><wicri:noRegion>Liaoning</wicri:noRegion></affiliation></author><author><name sortKey="Li, Xia" sort="Li, Xia" uniqKey="Li X" first="Xia" last="Li">Xia Li</name><affiliation wicri:level="1"><nlm:affiliation>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning</wicri:regionArea><wicri:noRegion>Liaoning</wicri:noRegion></affiliation></author></analytic><series><title level="j">Aging</title><idno type="eISSN">1945-4589</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Premature senescence of bone marrow-derived mesenchymal stem cells (BMSC) remains a major concern for their application clinically. Hedgehog signaling has been reported to regulate aging-associated markers and MSC skewed differentiation. Indian Hedgehog (IHH) is a ligand of Hedgehog intracellular pathway considered as an inducer in chondrogenesis of human BMSC. However, the role of IHH in the aging of BMSC is still unclear. This study explored the role IHH in the senescence of BMSC obtained from human samples and senescent mice. Isolated BMSC were transfected with IHH siRNA or incubated with exogenous IHH protein and the mechanisms of aging and differentiation investigated. Moreover, the interactions between IHH, and mammalian target of rapamycin (mTOR) and reactive oxygen species (ROS) were evaluated using the corresponding inhibitors and antioxidants. BMSC transfected with IHH siRNA showed characteristics of senescence-associated features including increased senescence-associated β-galactosidase activity (SA-β-gal), induction of cell cycle inhibitors (p53/p16), development of senescence-associated secretory phenotype (SASP), activation of ROS and mTOR pathways as well as the promotion of skewed differentiation. Interestingly, BMSC treatment with IHH protein reversed the senescence markers and corrected biased differentiation. Moreover, IHH shortage-induced senescence signs were compromised after mTOR and ROS inhibition. Our findings presented anti-aging activity for IHH in BMSC through down-regulation of ROS/mTOR pathways. This discovery might contribute to increasing the therapeutic, immunomodulatory and regenerative potency of BMSC and introduce a novel remedy in the management of aging-related diseases.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">32235006</PMID><DateRevised><Year>2020</Year><Month>09</Month><Day>29</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1945-4589</ISSN><JournalIssue CitedMedium="Internet"><Volume>12</Volume><Issue>7</Issue><PubDate><Year>2020</Year><Month>04</Month><Day>01</Day></PubDate></JournalIssue><Title>Aging</Title><ISOAbbreviation>Aging (Albany NY)</ISOAbbreviation></Journal><ArticleTitle>Indian Hedgehog regulates senescence in bone marrow-derived mesenchymal stem cell through modulation of ROS/mTOR/4EBP1, p70S6K1/2 pathway.</ArticleTitle><Pagination><MedlinePgn>5693-5715</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.18632/aging.102958</ELocationID><Abstract><AbstractText>Premature senescence of bone marrow-derived mesenchymal stem cells (BMSC) remains a major concern for their application clinically. Hedgehog signaling has been reported to regulate aging-associated markers and MSC skewed differentiation. Indian Hedgehog (IHH) is a ligand of Hedgehog intracellular pathway considered as an inducer in chondrogenesis of human BMSC. However, the role of IHH in the aging of BMSC is still unclear. This study explored the role IHH in the senescence of BMSC obtained from human samples and senescent mice. Isolated BMSC were transfected with IHH siRNA or incubated with exogenous IHH protein and the mechanisms of aging and differentiation investigated. Moreover, the interactions between IHH, and mammalian target of rapamycin (mTOR) and reactive oxygen species (ROS) were evaluated using the corresponding inhibitors and antioxidants. BMSC transfected with IHH siRNA showed characteristics of senescence-associated features including increased senescence-associated β-galactosidase activity (SA-β-gal), induction of cell cycle inhibitors (p53/p16), development of senescence-associated secretory phenotype (SASP), activation of ROS and mTOR pathways as well as the promotion of skewed differentiation. Interestingly, BMSC treatment with IHH protein reversed the senescence markers and corrected biased differentiation. Moreover, IHH shortage-induced senescence signs were compromised after mTOR and ROS inhibition. Our findings presented anti-aging activity for IHH in BMSC through down-regulation of ROS/mTOR pathways. This discovery might contribute to increasing the therapeutic, immunomodulatory and regenerative potency of BMSC and introduce a novel remedy in the management of aging-related diseases.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Al-Azab</LastName><ForeName>Mahmoud</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Immunology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Bing</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Elkhider</LastName><ForeName>Abdalkhalig</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Walana</LastName><ForeName>Williams</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Clinical Microbiology, University for Development Studies, Tamale, Ghana.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Weiping</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yuan</LastName><ForeName>Bo</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ye</LastName><ForeName>Yunshan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tang</LastName><ForeName>Yawei</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Almoiliqy</LastName><ForeName>Marwan</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Pharmacology, College of Pharmacy, Dalian Medical University, Liaoning, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Adlat</LastName><ForeName>Salah</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Key Laboratory of Molecular Epigenetics of MOE, School of Life Science, Northeast Normal University, Changchun, Jilin Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wei</LastName><ForeName>Jing</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Yan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Rheumatology and Immunology, The Second Affiliated Hospital of Dalian Medical University, Liaoning, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Xia</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, China.</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>2020</Year><Month>04</Month><Day>01</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Aging (Albany NY)</MedlineTA><NlmUniqueID>101508617</NlmUniqueID><ISSNLinking>1945-4589</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">Indian hedgehog</Keyword><Keyword MajorTopicYN="Y">aging</Keyword><Keyword MajorTopicYN="Y">differentiation</Keyword><Keyword MajorTopicYN="Y">mammalian target of rapamycin</Keyword><Keyword MajorTopicYN="Y">mesenchymal stem cell</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>04</Month><Day>04</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>02</Month><Day>19</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>4</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>4</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>4</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32235006</ArticleId><ArticleId IdType="doi">10.18632/aging.102958</ArticleId><ArticleId IdType="pii">102958</ArticleId><ArticleId IdType="pmc">PMC7185126</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Ghana</li><li>République populaire de Chine</li></country><region><li>Guangdong</li></region><settlement><li>Jiangmen</li></settlement></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Al Azab, Mahmoud" sort="Al Azab, Mahmoud" uniqKey="Al Azab M" first="Mahmoud" last="Al-Azab">Mahmoud Al-Azab</name></noRegion><name sortKey="Adlat, Salah" sort="Adlat, Salah" uniqKey="Adlat S" first="Salah" last="Adlat">Salah Adlat</name><name sortKey="Al Azab, Mahmoud" sort="Al Azab, Mahmoud" uniqKey="Al Azab M" first="Mahmoud" last="Al-Azab">Mahmoud Al-Azab</name><name sortKey="Almoiliqy, Marwan" sort="Almoiliqy, Marwan" uniqKey="Almoiliqy M" first="Marwan" last="Almoiliqy">Marwan Almoiliqy</name><name sortKey="Elkhider, Abdalkhalig" sort="Elkhider, Abdalkhalig" uniqKey="Elkhider A" first="Abdalkhalig" last="Elkhider">Abdalkhalig Elkhider</name><name sortKey="Li, Weiping" sort="Li, Weiping" uniqKey="Li W" first="Weiping" last="Li">Weiping Li</name><name sortKey="Li, Xia" sort="Li, Xia" uniqKey="Li X" first="Xia" last="Li">Xia Li</name><name sortKey="Tang, Yawei" sort="Tang, Yawei" uniqKey="Tang Y" first="Yawei" last="Tang">Yawei Tang</name><name sortKey="Walana, Williams" sort="Walana, Williams" uniqKey="Walana W" first="Williams" last="Walana">Williams Walana</name><name sortKey="Wang, Bing" sort="Wang, Bing" uniqKey="Wang B" first="Bing" last="Wang">Bing Wang</name><name sortKey="Wei, Jing" sort="Wei, Jing" uniqKey="Wei J" first="Jing" last="Wei">Jing Wei</name><name sortKey="Ye, Yunshan" sort="Ye, Yunshan" uniqKey="Ye Y" first="Yunshan" last="Ye">Yunshan Ye</name><name sortKey="Yuan, Bo" sort="Yuan, Bo" uniqKey="Yuan B" first="Bo" last="Yuan">Bo Yuan</name><name sortKey="Zhang, Yan" sort="Zhang, Yan" uniqKey="Zhang Y" first="Yan" last="Zhang">Yan Zhang</name></country><country name="Ghana"><noRegion><name sortKey="Walana, Williams" sort="Walana, Williams" uniqKey="Walana W" first="Williams" last="Walana">Williams Walana</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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