Olig2-Induced Neural Stem Cell Differentiation Involves Downregulation of Wnt Signaling and Induction of Dickkopf-1 Expression
Identifieur interne : 002161 ( Main/Exploration ); précédent : 002160; suivant : 002162Olig2-Induced Neural Stem Cell Differentiation Involves Downregulation of Wnt Signaling and Induction of Dickkopf-1 Expression
Auteurs : Sung-Min Ahn [Corée du Sud] ; Kyunghee Byun [Corée du Sud] ; Deokhoon Kim [Corée du Sud] ; Kiyoung Lee [Corée du Sud] ; Jong Shin Yoo [Corée du Sud] ; Seung U. Kim [Corée du Sud, Canada] ; Eek-Hoon Jho [Corée du Sud] ; Richard J. Simpson [Australie] ; Bonghee Lee [Corée du Sud]Source :
- PLoS ONE [ 1932-6203 ] ; 2008.
Abstract
Understanding stem cell-differentiation at the molecular level is important for clinical applications of stem cells and for finding new therapeutic approaches in the context of cancer stem cells. To investigate genome-wide changes involved in differentiation, we have used immortalized neural stem cell (NSC) line (HB1.F3) and Olig2-induced NSC differentiation model (F3.Olig2). Using microarray analysis, we revealed that Olig2-induced NSC differentiation involves downregulation of Wnt pathway, which was further confirmed by TOPflash/FOPflash reporter assay, RT-PCR analysis, immunoblots, and immunocytochemistry. Furthermore, we found that Olig2-induced differentiation induces the expression of Dickkopf-1(Dkk1), a potent antagonist of Wnt signaling. Dkk1 treatment blocked Wnt signaling in HB1.F3 in a dosage-dependent manner, and induced differentiation into astrocytes, oligodendrocytes, and neurons. Our results support cancer stem cell hypothesis which implies that signaling pathway for self-renewal and proliferation of stem cells is maintained till the late stage of differentiation. In our proposed model, Dkk1 may play an important role in downregulating self-renewal and proliferation pathway of stem cells at the late stage of differentiation, and its failure may lead to carcinogenesis.
Url:
DOI: 10.1371/journal.pone.0003917
PubMed: 19093005
PubMed Central: 2602983
Affiliations:
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Science, Incheon, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Center for Genomics and Proteomics, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon</wicri:regionArea><wicri:noRegion>Incheon</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Kiyoung" sort="Lee, Kiyoung" uniqKey="Lee K" first="Kiyoung" last="Lee">Kiyoung Lee</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Center for Genomics and Proteomics, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Center for Genomics and Proteomics, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon</wicri:regionArea><wicri:noRegion>Incheon</wicri:noRegion></affiliation></author><author><name sortKey="Yoo, Jong Shin" sort="Yoo, Jong Shin" uniqKey="Yoo J" first="Jong Shin" last="Yoo">Jong Shin Yoo</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Mass Spectrometry Analysis Group, Korea Basic Science Institute, Daejeon, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Mass Spectrometry Analysis Group, Korea Basic Science Institute, Daejeon</wicri:regionArea><wicri:noRegion>Daejeon</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U." last="Kim">Seung U. Kim</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Gachon Institute for Regenerative Medicine, Gachon University of Medicine and Science, Incheon, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Gachon Institute for Regenerative Medicine, Gachon University of Medicine and Science, Incheon</wicri:regionArea><wicri:noRegion>Incheon</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Department of Medicine, University of British Columbia, Vancouver, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Medicine, University of British Columbia, Vancouver</wicri:regionArea><wicri:noRegion>Vancouver</wicri:noRegion></affiliation></author><author><name sortKey="Jho, Eek Hoon" sort="Jho, Eek Hoon" uniqKey="Jho E" first="Eek-Hoon" last="Jho">Eek-Hoon Jho</name><affiliation wicri:level="3"><nlm:aff id="aff5"><addr-line>Department of Life Science, The University of Seoul, Dongdaemun-gu, Seoul, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Life Science, The University of Seoul, Dongdaemun-gu, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement></placeName></affiliation></author><author><name sortKey="Simpson, Richard J" sort="Simpson, Richard J" uniqKey="Simpson R" first="Richard J." last="Simpson">Richard J. 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To investigate genome-wide changes involved in differentiation, we have used immortalized neural stem cell (NSC) line (HB1.F3) and Olig2-induced NSC differentiation model (F3.Olig2). Using microarray analysis, we revealed that Olig2-induced NSC differentiation involves downregulation of Wnt pathway, which was further confirmed by TOPflash/FOPflash reporter assay, RT-PCR analysis, immunoblots, and immunocytochemistry. Furthermore, we found that Olig2-induced differentiation induces the expression of Dickkopf-1(Dkk1), a potent antagonist of Wnt signaling. Dkk1 treatment blocked Wnt signaling in HB1.F3 in a dosage-dependent manner, and induced differentiation into astrocytes, oligodendrocytes, and neurons. Our results support cancer stem cell hypothesis which implies that signaling pathway for self-renewal and proliferation of stem cells is maintained till the late stage of differentiation. In our proposed model, Dkk1 may play an important role in downregulating self-renewal and proliferation pathway of stem cells at the late stage of differentiation, and its failure may lead to carcinogenesis.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Australie</li><li>Canada</li><li>Corée du Sud</li></country><settlement><li>Séoul</li></settlement></list><tree><country name="Corée du Sud"><noRegion><name sortKey="Ahn, Sung Min" sort="Ahn, Sung Min" uniqKey="Ahn S" first="Sung-Min" last="Ahn">Sung-Min Ahn</name></noRegion><name sortKey="Byun, Kyunghee" sort="Byun, Kyunghee" uniqKey="Byun K" first="Kyunghee" last="Byun">Kyunghee Byun</name><name sortKey="Jho, Eek Hoon" sort="Jho, Eek Hoon" uniqKey="Jho E" first="Eek-Hoon" last="Jho">Eek-Hoon Jho</name><name sortKey="Kim, Deokhoon" sort="Kim, Deokhoon" uniqKey="Kim D" first="Deokhoon" last="Kim">Deokhoon Kim</name><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U." last="Kim">Seung U. Kim</name><name sortKey="Lee, Bonghee" sort="Lee, Bonghee" uniqKey="Lee B" first="Bonghee" last="Lee">Bonghee Lee</name><name sortKey="Lee, Kiyoung" sort="Lee, Kiyoung" uniqKey="Lee K" first="Kiyoung" last="Lee">Kiyoung Lee</name><name sortKey="Yoo, Jong Shin" sort="Yoo, Jong Shin" uniqKey="Yoo J" first="Jong Shin" last="Yoo">Jong Shin Yoo</name></country><country name="Canada"><noRegion><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U." last="Kim">Seung U. Kim</name></noRegion></country><country name="Australie"><noRegion><name sortKey="Simpson, Richard J" sort="Simpson, Richard J" uniqKey="Simpson R" first="Richard J." last="Simpson">Richard J. Simpson</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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