Inhibition of Transforming Growth Factor β (TGF-β) Signaling can Substitute for Oct4 Protein in Reprogramming and Maintain Pluripotency
Mouse pluripotent stem cells (PSCs), such as ES cells and induced PSCs (iPSCs), are an excellent system to investigate the molecular and cellular mechanisms involved in early embryonic development. The signaling pathways orchestrated by leukemia inhibitor factor/STAT3, Wnt/β-catenin, and FGF/MEK/ERK...
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| Veröffentlicht in: | The Journal of biological chemistry 2015-02, Vol.290 (7), p.4500-4511 |
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| creator | Tan, Fangzhi Qian, Cheng Tang, Ke Abd-Allah, Saber Mohamed Jing, Naihe |
| description | Mouse pluripotent stem cells (PSCs), such as ES cells and induced PSCs (iPSCs), are an excellent system to investigate the molecular and cellular mechanisms involved in early embryonic development. The signaling pathways orchestrated by leukemia inhibitor factor/STAT3, Wnt/β-catenin, and FGF/MEK/ERK play key roles in the generation of pluripotency. However, the function of TGF-β signaling in this process remains elusive. Here we show that inhibiting TGF-β signaling with its inhibitor SB431542 can substitute for Oct4 during reprogramming. Moreover, inhibiting TGF-β signaling can sustain the pluripotency of iPSCs and ES cells through modulating FGF/MEK/ERK signaling. Therefore, this study reveals a novel function of TGF-β signaling inhibition in the generation and maintenance of PSCs.
Background: Pluripotent stem cells (PSCs) have been used widely to study molecular mechanisms involved in early embryo development.
Results: The TGF-β inhibitor SB431542 substitutes for Oct4 in reprogramming and maintains pluripotency.
Conclusion: TGF-β signaling inhibition promotes generation and maintenance of PSCs.
Significance: Our study reveals a novel function of TGF-β signaling in the generation of PSCs. |
| doi_str_mv | 10.1074/jbc.M114.609016 |
| format | Article |
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Background: Pluripotent stem cells (PSCs) have been used widely to study molecular mechanisms involved in early embryo development.
Results: The TGF-β inhibitor SB431542 substitutes for Oct4 in reprogramming and maintains pluripotency.
Conclusion: TGF-β signaling inhibition promotes generation and maintenance of PSCs.
Significance: Our study reveals a novel function of TGF-β signaling in the generation of PSCs.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M114.609016</identifier><identifier>PMID: 25548277</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Benzamides - pharmacology ; Blotting, Western ; Cell Biology ; Cell Differentiation - drug effects ; Cells, Cultured ; Cellular Reprogramming - drug effects ; Dioxoles - pharmacology ; Embryo, Mammalian - cytology ; Embryo, Mammalian - drug effects ; Embryo, Mammalian - metabolism ; Embryonic Stem Cells - cytology ; Embryonic Stem Cells - drug effects ; Embryonic Stem Cells - metabolism ; ERK ; ES Cell ; Extracellular Signal-Regulated MAP Kinases - genetics ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Fibroblast Growth Factor 1 - genetics ; Fibroblast Growth Factor 1 - metabolism ; Fibroblasts - cytology ; Fibroblasts - drug effects ; Fibroblasts - metabolism ; Fluorescent Antibody Technique ; Induced Pluripotent Stem Cell (iPSC) ; Induced Pluripotent Stem Cells - cytology ; Induced Pluripotent Stem Cells - drug effects ; Induced Pluripotent Stem Cells - metabolism ; MAP Kinase Kinase 1 - genetics ; MAP Kinase Kinase 1 - metabolism ; Mice ; Mice, Inbred C57BL ; Oct4 ; Octamer Transcription Factor-3 - genetics ; Octamer Transcription Factor-3 - metabolism ; Real-Time Polymerase Chain Reaction ; Reprogramming ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; Signal Transduction - drug effects ; TGF-β ; Transforming Growth Factor beta - antagonists & inhibitors</subject><ispartof>The Journal of biological chemistry, 2015-02, Vol.290 (7), p.4500-4511</ispartof><rights>2015 © 2015 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><rights>2015 by The American Society for Biochemistry and Molecular Biology, Inc.</rights><rights>2015 by The American Society for Biochemistry and Molecular Biology, Inc. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c443t-355603bdca2edb69876614c18c7337006c217c7e10a47d49d4e3977b9f5aae2a3</citedby><cites>FETCH-LOGICAL-c443t-355603bdca2edb69876614c18c7337006c217c7e10a47d49d4e3977b9f5aae2a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326853/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326853/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,728,781,785,886,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25548277$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tan, Fangzhi</creatorcontrib><creatorcontrib>Qian, Cheng</creatorcontrib><creatorcontrib>Tang, Ke</creatorcontrib><creatorcontrib>Abd-Allah, Saber Mohamed</creatorcontrib><creatorcontrib>Jing, Naihe</creatorcontrib><title>Inhibition of Transforming Growth Factor β (TGF-β) Signaling can Substitute for Oct4 Protein in Reprogramming and Maintain Pluripotency</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Mouse pluripotent stem cells (PSCs), such as ES cells and induced PSCs (iPSCs), are an excellent system to investigate the molecular and cellular mechanisms involved in early embryonic development. The signaling pathways orchestrated by leukemia inhibitor factor/STAT3, Wnt/β-catenin, and FGF/MEK/ERK play key roles in the generation of pluripotency. However, the function of TGF-β signaling in this process remains elusive. Here we show that inhibiting TGF-β signaling with its inhibitor SB431542 can substitute for Oct4 during reprogramming. Moreover, inhibiting TGF-β signaling can sustain the pluripotency of iPSCs and ES cells through modulating FGF/MEK/ERK signaling. Therefore, this study reveals a novel function of TGF-β signaling inhibition in the generation and maintenance of PSCs.
Background: Pluripotent stem cells (PSCs) have been used widely to study molecular mechanisms involved in early embryo development.
Results: The TGF-β inhibitor SB431542 substitutes for Oct4 in reprogramming and maintains pluripotency.
Conclusion: TGF-β signaling inhibition promotes generation and maintenance of PSCs.
Significance: Our study reveals a novel function of TGF-β signaling in the generation of PSCs.</description><subject>Animals</subject><subject>Benzamides - pharmacology</subject><subject>Blotting, Western</subject><subject>Cell Biology</subject><subject>Cell Differentiation - drug effects</subject><subject>Cells, Cultured</subject><subject>Cellular Reprogramming - drug effects</subject><subject>Dioxoles - pharmacology</subject><subject>Embryo, Mammalian - cytology</subject><subject>Embryo, Mammalian - drug effects</subject><subject>Embryo, Mammalian - metabolism</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Embryonic Stem Cells - drug effects</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>ERK</subject><subject>ES Cell</subject><subject>Extracellular Signal-Regulated MAP Kinases - genetics</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Fibroblast Growth Factor 1 - genetics</subject><subject>Fibroblast Growth Factor 1 - metabolism</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - drug effects</subject><subject>Fibroblasts - metabolism</subject><subject>Fluorescent Antibody Technique</subject><subject>Induced Pluripotent Stem Cell (iPSC)</subject><subject>Induced Pluripotent Stem Cells - cytology</subject><subject>Induced Pluripotent Stem Cells - drug effects</subject><subject>Induced Pluripotent Stem Cells - metabolism</subject><subject>MAP Kinase Kinase 1 - genetics</subject><subject>MAP Kinase Kinase 1 - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Oct4</subject><subject>Octamer Transcription Factor-3 - genetics</subject><subject>Octamer Transcription Factor-3 - metabolism</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Reprogramming</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>Signal Transduction - drug effects</subject><subject>TGF-β</subject><subject>Transforming Growth Factor beta - antagonists & inhibitors</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1KAzEUhYMoWn_W7iRLXUxNJpnJzEaQYmuhRbEV3IVMJjONTJOSSRUfwdfpg_SZTK2KLrzkkkXO-S43B4BTjLoYMXr5XMjuGGPaTVGOcLoDOhhlJCIJftoFHYRiHOVxkh2Aw7Z9RqFojvfBQZwkNIsZ64D3oZnpQnttDbQVnDph2sq6uTY1HDj76mewL6S3Dq5X8Hw66Efr1QWc6NqIZqORwsDJsmi99kuvYLDCO-kpvHfWK21gOA9q4WztxPwTKkwJx0IbHxreN0unF0Fp5Nsx2KtE06qTr_sIPPZvpr3baHQ3GPauR5GklPiwWpIiUpRSxKos0jxjaYqpxJlkhDCEUhljJpnCSFBW0rykiuSMFXmVCKFiQY7A1Za7WBZzVUplvBMNXzg9F-6NW6H53xejZ7y2L5ySOM0SEgCXW4B0tm2dqn68GPFNKjykwjep8G0qwXH2e-SP_juGIMi3AhUWf9HK8Vbq8Cmq1E5Jz0ur_4V_AGSIoCE</recordid><startdate>20150213</startdate><enddate>20150213</enddate><creator>Tan, Fangzhi</creator><creator>Qian, Cheng</creator><creator>Tang, Ke</creator><creator>Abd-Allah, Saber Mohamed</creator><creator>Jing, Naihe</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20150213</creationdate><title>Inhibition of Transforming Growth Factor β (TGF-β) Signaling can Substitute for Oct4 Protein in Reprogramming and Maintain Pluripotency</title><author>Tan, Fangzhi ; Qian, Cheng ; Tang, Ke ; Abd-Allah, Saber Mohamed ; Jing, Naihe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c443t-355603bdca2edb69876614c18c7337006c217c7e10a47d49d4e3977b9f5aae2a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Benzamides - pharmacology</topic><topic>Blotting, Western</topic><topic>Cell Biology</topic><topic>Cell Differentiation - drug effects</topic><topic>Cells, Cultured</topic><topic>Cellular Reprogramming - drug effects</topic><topic>Dioxoles - pharmacology</topic><topic>Embryo, Mammalian - cytology</topic><topic>Embryo, Mammalian - drug effects</topic><topic>Embryo, Mammalian - metabolism</topic><topic>Embryonic Stem Cells - cytology</topic><topic>Embryonic Stem Cells - drug effects</topic><topic>Embryonic Stem Cells - metabolism</topic><topic>ERK</topic><topic>ES Cell</topic><topic>Extracellular Signal-Regulated MAP Kinases - genetics</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Fibroblast Growth Factor 1 - genetics</topic><topic>Fibroblast Growth Factor 1 - metabolism</topic><topic>Fibroblasts - cytology</topic><topic>Fibroblasts - drug effects</topic><topic>Fibroblasts - metabolism</topic><topic>Fluorescent Antibody Technique</topic><topic>Induced Pluripotent Stem Cell (iPSC)</topic><topic>Induced Pluripotent Stem Cells - cytology</topic><topic>Induced Pluripotent Stem Cells - drug effects</topic><topic>Induced Pluripotent Stem Cells - metabolism</topic><topic>MAP Kinase Kinase 1 - genetics</topic><topic>MAP Kinase Kinase 1 - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Oct4</topic><topic>Octamer Transcription Factor-3 - genetics</topic><topic>Octamer Transcription Factor-3 - metabolism</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Reprogramming</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - genetics</topic><topic>Signal Transduction - drug effects</topic><topic>TGF-β</topic><topic>Transforming Growth Factor beta - antagonists & inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tan, Fangzhi</creatorcontrib><creatorcontrib>Qian, Cheng</creatorcontrib><creatorcontrib>Tang, Ke</creatorcontrib><creatorcontrib>Abd-Allah, Saber Mohamed</creatorcontrib><creatorcontrib>Jing, Naihe</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tan, Fangzhi</au><au>Qian, Cheng</au><au>Tang, Ke</au><au>Abd-Allah, Saber Mohamed</au><au>Jing, Naihe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of Transforming Growth Factor β (TGF-β) Signaling can Substitute for Oct4 Protein in Reprogramming and Maintain Pluripotency</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2015-02-13</date><risdate>2015</risdate><volume>290</volume><issue>7</issue><spage>4500</spage><epage>4511</epage><pages>4500-4511</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Mouse pluripotent stem cells (PSCs), such as ES cells and induced PSCs (iPSCs), are an excellent system to investigate the molecular and cellular mechanisms involved in early embryonic development. The signaling pathways orchestrated by leukemia inhibitor factor/STAT3, Wnt/β-catenin, and FGF/MEK/ERK play key roles in the generation of pluripotency. However, the function of TGF-β signaling in this process remains elusive. Here we show that inhibiting TGF-β signaling with its inhibitor SB431542 can substitute for Oct4 during reprogramming. Moreover, inhibiting TGF-β signaling can sustain the pluripotency of iPSCs and ES cells through modulating FGF/MEK/ERK signaling. Therefore, this study reveals a novel function of TGF-β signaling inhibition in the generation and maintenance of PSCs.
Background: Pluripotent stem cells (PSCs) have been used widely to study molecular mechanisms involved in early embryo development.
Results: The TGF-β inhibitor SB431542 substitutes for Oct4 in reprogramming and maintains pluripotency.
Conclusion: TGF-β signaling inhibition promotes generation and maintenance of PSCs.
Significance: Our study reveals a novel function of TGF-β signaling in the generation of PSCs.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>25548277</pmid><doi>10.1074/jbc.M114.609016</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Animals Benzamides - pharmacology Blotting, Western Cell Biology Cell Differentiation - drug effects Cells, Cultured Cellular Reprogramming - drug effects Dioxoles - pharmacology Embryo, Mammalian - cytology Embryo, Mammalian - drug effects Embryo, Mammalian - metabolism Embryonic Stem Cells - cytology Embryonic Stem Cells - drug effects Embryonic Stem Cells - metabolism ERK ES Cell Extracellular Signal-Regulated MAP Kinases - genetics Extracellular Signal-Regulated MAP Kinases - metabolism Fibroblast Growth Factor 1 - genetics Fibroblast Growth Factor 1 - metabolism Fibroblasts - cytology Fibroblasts - drug effects Fibroblasts - metabolism Fluorescent Antibody Technique Induced Pluripotent Stem Cell (iPSC) Induced Pluripotent Stem Cells - cytology Induced Pluripotent Stem Cells - drug effects Induced Pluripotent Stem Cells - metabolism MAP Kinase Kinase 1 - genetics MAP Kinase Kinase 1 - metabolism Mice Mice, Inbred C57BL Oct4 Octamer Transcription Factor-3 - genetics Octamer Transcription Factor-3 - metabolism Real-Time Polymerase Chain Reaction Reprogramming Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics Signal Transduction - drug effects TGF-β Transforming Growth Factor beta - antagonists & inhibitors |
| title | Inhibition of Transforming Growth Factor β (TGF-β) Signaling can Substitute for Oct4 Protein in Reprogramming and Maintain Pluripotency |
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