The novel application of cordycepin in maintaining stem cell pluripotency and increasing iPS cell generation efficiency
Maintaining the pluripotency of either embryonic stem (ES) cells or induced pluripotent stem (iPS) cells is a fundamental part of stem cell research. In this study, we reported that cordycepin promoted the expression of pluripotency markers in ES and iPS cells. ES cells treated with cordycepin demon...
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| Veröffentlicht in: | Scientific reports 2020-02, Vol.10 (1), p.2187, Article 2187 |
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| description | Maintaining the pluripotency of either embryonic stem (ES) cells or induced pluripotent stem (iPS) cells is a fundamental part of stem cell research. In this study, we reported that cordycepin promoted the expression of pluripotency markers in ES and iPS cells. ES cells treated with cordycepin demonstrated their potential for generating embryoid bodies and differentiating into all three germ layers. The expression levels of phospho-Jak2, phospho-Stat3, integrin αV, and integrin β5 were increased after cordycepin treatment. Furthermore, the protein expression levels of IL-6 family proteins (IL-6, IL-11, LIF, oncostatin M (OSM), ciliary neurotrophic factor (CNTF)), and epidermal growth factor (EGF) were also upregulated after cordycepin treatment, but were restored after co-treatment with a Jak2 inhibitor (AG490). The gene expression levels of Yamanaka factors were upregulated in mouse embryonic fibroblasts (MEFs) after cordycepin treatment. Moreover, the generation efficiencies of iPS cells were elevated after cordycepin treatment. We found that iPS cells generated after cordycepin treatment, not only expressed pluripotency markers, but also showed the ability of differentiating into neuron stem/progenitor cells. Taken together, we demonstrated that cordycepin maintained the pluripotency of stem cells via regulation of extracellular matrix (ECM) and Jak2/Stat3 signaling pathway and improved the generation efficiency of iPSCs. |
| doi_str_mv | 10.1038/s41598-020-59154-5 |
| format | Article |
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In this study, we reported that cordycepin promoted the expression of pluripotency markers in ES and iPS cells. ES cells treated with cordycepin demonstrated their potential for generating embryoid bodies and differentiating into all three germ layers. The expression levels of phospho-Jak2, phospho-Stat3, integrin αV, and integrin β5 were increased after cordycepin treatment. Furthermore, the protein expression levels of IL-6 family proteins (IL-6, IL-11, LIF, oncostatin M (OSM), ciliary neurotrophic factor (CNTF)), and epidermal growth factor (EGF) were also upregulated after cordycepin treatment, but were restored after co-treatment with a Jak2 inhibitor (AG490). The gene expression levels of Yamanaka factors were upregulated in mouse embryonic fibroblasts (MEFs) after cordycepin treatment. Moreover, the generation efficiencies of iPS cells were elevated after cordycepin treatment. We found that iPS cells generated after cordycepin treatment, not only expressed pluripotency markers, but also showed the ability of differentiating into neuron stem/progenitor cells. Taken together, we demonstrated that cordycepin maintained the pluripotency of stem cells via regulation of extracellular matrix (ECM) and Jak2/Stat3 signaling pathway and improved the generation efficiency of iPSCs.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-59154-5</identifier><identifier>PMID: 32042022</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/100 ; 631/532/2064/2158 ; 631/532/2435 ; Animals ; Cell differentiation ; Cell Differentiation - genetics ; Cells, Cultured ; Ciliary neurotrophic factor ; Cordycepin ; Deoxyadenosines - metabolism ; Deoxyadenosines - pharmacology ; Embryo fibroblasts ; Embryoid Bodies - metabolism ; Embryonic Stem Cells - metabolism ; Epidermal growth factor ; Extracellular matrix ; Fibroblasts - metabolism ; Gene expression ; Humanities and Social Sciences ; Induced Pluripotent Stem Cells - drug effects ; Induced Pluripotent Stem Cells - metabolism ; Inhibitory postsynaptic potentials ; Integrins - metabolism ; Interleukin 11 ; Interleukin 6 ; Janus kinase 2 ; Janus Kinase 2 - metabolism ; Mice ; multidisciplinary ; Oncostatin M ; Pluripotency ; Pluripotent Stem Cells - drug effects ; Pluripotent Stem Cells - metabolism ; Progenitor cells ; Science ; Science (multidisciplinary) ; Signal Transduction ; SOXB1 Transcription Factors - metabolism ; Stat3 protein ; STAT3 Transcription Factor - metabolism ; Stem cell transplantation ; Stem cells</subject><ispartof>Scientific reports, 2020-02, Vol.10 (1), p.2187, Article 2187</ispartof><rights>The Author(s) 2020</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c577t-f97367861fccd60646ccc30f8664860601f18dc45a31779fda4f81c9d19567e03</citedby><cites>FETCH-LOGICAL-c577t-f97367861fccd60646ccc30f8664860601f18dc45a31779fda4f81c9d19567e03</cites><orcidid>0000-0002-9480-8224</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010772/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010772/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32042022$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Chie-Hong</creatorcontrib><creatorcontrib>Chang, Cheng-Hsuan</creatorcontrib><creatorcontrib>Lin, Tsung-Li</creatorcontrib><creatorcontrib>Fu, Ru-Huei</creatorcontrib><creatorcontrib>Huang, Yu-Chuen</creatorcontrib><creatorcontrib>Chen, Shih-Yin</creatorcontrib><creatorcontrib>Shyu, Woei-Cherng</creatorcontrib><creatorcontrib>Liu, Shih-Ping</creatorcontrib><title>The novel application of cordycepin in maintaining stem cell pluripotency and increasing iPS cell generation efficiency</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Maintaining the pluripotency of either embryonic stem (ES) cells or induced pluripotent stem (iPS) cells is a fundamental part of stem cell research. In this study, we reported that cordycepin promoted the expression of pluripotency markers in ES and iPS cells. ES cells treated with cordycepin demonstrated their potential for generating embryoid bodies and differentiating into all three germ layers. The expression levels of phospho-Jak2, phospho-Stat3, integrin αV, and integrin β5 were increased after cordycepin treatment. Furthermore, the protein expression levels of IL-6 family proteins (IL-6, IL-11, LIF, oncostatin M (OSM), ciliary neurotrophic factor (CNTF)), and epidermal growth factor (EGF) were also upregulated after cordycepin treatment, but were restored after co-treatment with a Jak2 inhibitor (AG490). The gene expression levels of Yamanaka factors were upregulated in mouse embryonic fibroblasts (MEFs) after cordycepin treatment. Moreover, the generation efficiencies of iPS cells were elevated after cordycepin treatment. We found that iPS cells generated after cordycepin treatment, not only expressed pluripotency markers, but also showed the ability of differentiating into neuron stem/progenitor cells. Taken together, we demonstrated that cordycepin maintained the pluripotency of stem cells via regulation of extracellular matrix (ECM) and Jak2/Stat3 signaling pathway and improved the generation efficiency of iPSCs.</description><subject>13/100</subject><subject>631/532/2064/2158</subject><subject>631/532/2435</subject><subject>Animals</subject><subject>Cell differentiation</subject><subject>Cell Differentiation - genetics</subject><subject>Cells, Cultured</subject><subject>Ciliary neurotrophic factor</subject><subject>Cordycepin</subject><subject>Deoxyadenosines - metabolism</subject><subject>Deoxyadenosines - pharmacology</subject><subject>Embryo fibroblasts</subject><subject>Embryoid Bodies - metabolism</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>Epidermal growth factor</subject><subject>Extracellular matrix</subject><subject>Fibroblasts - metabolism</subject><subject>Gene expression</subject><subject>Humanities and Social Sciences</subject><subject>Induced Pluripotent Stem Cells - 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genetics</topic><topic>Cells, Cultured</topic><topic>Ciliary neurotrophic factor</topic><topic>Cordycepin</topic><topic>Deoxyadenosines - metabolism</topic><topic>Deoxyadenosines - pharmacology</topic><topic>Embryo fibroblasts</topic><topic>Embryoid Bodies - metabolism</topic><topic>Embryonic Stem Cells - metabolism</topic><topic>Epidermal growth factor</topic><topic>Extracellular matrix</topic><topic>Fibroblasts - metabolism</topic><topic>Gene expression</topic><topic>Humanities and Social Sciences</topic><topic>Induced Pluripotent Stem Cells - drug effects</topic><topic>Induced Pluripotent Stem Cells - metabolism</topic><topic>Inhibitory postsynaptic potentials</topic><topic>Integrins - metabolism</topic><topic>Interleukin 11</topic><topic>Interleukin 6</topic><topic>Janus kinase 2</topic><topic>Janus Kinase 2 - metabolism</topic><topic>Mice</topic><topic>multidisciplinary</topic><topic>Oncostatin M</topic><topic>Pluripotency</topic><topic>Pluripotent Stem Cells - drug effects</topic><topic>Pluripotent Stem Cells - metabolism</topic><topic>Progenitor cells</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Signal Transduction</topic><topic>SOXB1 Transcription Factors - metabolism</topic><topic>Stat3 protein</topic><topic>STAT3 Transcription Factor - metabolism</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Chie-Hong</creatorcontrib><creatorcontrib>Chang, Cheng-Hsuan</creatorcontrib><creatorcontrib>Lin, Tsung-Li</creatorcontrib><creatorcontrib>Fu, Ru-Huei</creatorcontrib><creatorcontrib>Huang, Yu-Chuen</creatorcontrib><creatorcontrib>Chen, Shih-Yin</creatorcontrib><creatorcontrib>Shyu, Woei-Cherng</creatorcontrib><creatorcontrib>Liu, Shih-Ping</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Chie-Hong</au><au>Chang, Cheng-Hsuan</au><au>Lin, Tsung-Li</au><au>Fu, Ru-Huei</au><au>Huang, Yu-Chuen</au><au>Chen, Shih-Yin</au><au>Shyu, Woei-Cherng</au><au>Liu, Shih-Ping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The novel application of cordycepin in maintaining stem cell pluripotency and increasing iPS cell generation efficiency</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-02-10</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>2187</spage><pages>2187-</pages><artnum>2187</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Maintaining the pluripotency of either embryonic stem (ES) cells or induced pluripotent stem (iPS) cells is a fundamental part of stem cell research. In this study, we reported that cordycepin promoted the expression of pluripotency markers in ES and iPS cells. ES cells treated with cordycepin demonstrated their potential for generating embryoid bodies and differentiating into all three germ layers. The expression levels of phospho-Jak2, phospho-Stat3, integrin αV, and integrin β5 were increased after cordycepin treatment. Furthermore, the protein expression levels of IL-6 family proteins (IL-6, IL-11, LIF, oncostatin M (OSM), ciliary neurotrophic factor (CNTF)), and epidermal growth factor (EGF) were also upregulated after cordycepin treatment, but were restored after co-treatment with a Jak2 inhibitor (AG490). The gene expression levels of Yamanaka factors were upregulated in mouse embryonic fibroblasts (MEFs) after cordycepin treatment. Moreover, the generation efficiencies of iPS cells were elevated after cordycepin treatment. We found that iPS cells generated after cordycepin treatment, not only expressed pluripotency markers, but also showed the ability of differentiating into neuron stem/progenitor cells. Taken together, we demonstrated that cordycepin maintained the pluripotency of stem cells via regulation of extracellular matrix (ECM) and Jak2/Stat3 signaling pathway and improved the generation efficiency of iPSCs.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32042022</pmid><doi>10.1038/s41598-020-59154-5</doi><orcidid>https://orcid.org/0000-0002-9480-8224</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 13/100 631/532/2064/2158 631/532/2435 Animals Cell differentiation Cell Differentiation - genetics Cells, Cultured Ciliary neurotrophic factor Cordycepin Deoxyadenosines - metabolism Deoxyadenosines - pharmacology Embryo fibroblasts Embryoid Bodies - metabolism Embryonic Stem Cells - metabolism Epidermal growth factor Extracellular matrix Fibroblasts - metabolism Gene expression Humanities and Social Sciences Induced Pluripotent Stem Cells - drug effects Induced Pluripotent Stem Cells - metabolism Inhibitory postsynaptic potentials Integrins - metabolism Interleukin 11 Interleukin 6 Janus kinase 2 Janus Kinase 2 - metabolism Mice multidisciplinary Oncostatin M Pluripotency Pluripotent Stem Cells - drug effects Pluripotent Stem Cells - metabolism Progenitor cells Science Science (multidisciplinary) Signal Transduction SOXB1 Transcription Factors - metabolism Stat3 protein STAT3 Transcription Factor - metabolism Stem cell transplantation Stem cells |
| title | The novel application of cordycepin in maintaining stem cell pluripotency and increasing iPS cell generation efficiency |
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