An Efficient and Reversible Transposable System for Gene Delivery and Lineage-Specific Differentiation in Human Embryonic Stem Cells
Unraveling the therapeutic potential of human embryonic stem cells (hESC) requires tools to modify their genome. We have engineered the PiggyBac transposable element to create an efficient system for gene delivery in hESCs. This redesigned system, named “ePiggyBac,” can deliver up to 18 Kb inserts,...
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| Veröffentlicht in: | Cell stem cell 2009-09, Vol.5 (3), p.332-342 |
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| creator | Lacoste, Arnaud Berenshteyn, Frada Brivanlou, Ali H. |
| description | Unraveling the therapeutic potential of human embryonic stem cells (hESC) requires tools to modify their genome. We have engineered the PiggyBac transposable element to create an efficient system for gene delivery in hESCs. This redesigned system, named “ePiggyBac,” can deliver up to 18 Kb inserts, and transgene expression is observed in almost 90% of hES cells. ePiggyBac transposons can also carry insulators, inducible expression cassettes, and short hairpin RNAs for gain- and loss-of-function approaches. In hES cells, ePiggyBac's efficiency is superior to that of viral vectors and previously described transposons, including other PiggyBac-based systems. In addition, ePiggyBac transgenes can be removed from the hESC genome without leaving any mutation. We used this system to direct hESC differentiation toward a neuronal phenotype. We then removed the transposons to obtain transgene-free neuronal precursors and neurons. The ability to create fully reversible genetic modifications represents an important step toward clinical applications of hESCs. |
| doi_str_mv | 10.1016/j.stem.2009.07.011 |
| format | Article |
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We have engineered the PiggyBac transposable element to create an efficient system for gene delivery in hESCs. This redesigned system, named “ePiggyBac,” can deliver up to 18 Kb inserts, and transgene expression is observed in almost 90% of hES cells. ePiggyBac transposons can also carry insulators, inducible expression cassettes, and short hairpin RNAs for gain- and loss-of-function approaches. In hES cells, ePiggyBac's efficiency is superior to that of viral vectors and previously described transposons, including other PiggyBac-based systems. In addition, ePiggyBac transgenes can be removed from the hESC genome without leaving any mutation. We used this system to direct hESC differentiation toward a neuronal phenotype. We then removed the transposons to obtain transgene-free neuronal precursors and neurons. The ability to create fully reversible genetic modifications represents an important step toward clinical applications of hESCs.</description><identifier>ISSN: 1934-5909</identifier><identifier>EISSN: 1875-9777</identifier><identifier>DOI: 10.1016/j.stem.2009.07.011</identifier><identifier>PMID: 19733544</identifier><language>eng</language><publisher>Cambridge, MA: Elsevier Inc</publisher><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Applied cell therapy and gene therapy ; Base Sequence ; Biological and medical sciences ; Biotechnology ; Cell Differentiation - drug effects ; Cell Lineage - drug effects ; DNA Transposable Elements - genetics ; Doxycycline - pharmacology ; Embryonic Stem Cells - cytology ; Embryonic Stem Cells - drug effects ; Embryonic Stem Cells - metabolism ; Fundamental and applied biological sciences. Psychology ; Gene therapy ; Gene Transfer Techniques ; Genetic Engineering ; Genome, Human - genetics ; Health. Pharmaceutical industry ; Humans ; Industrial applications and implications. Economical aspects ; Macaca ; Medical sciences ; Molecular Sequence Data ; Mutagenesis, Insertional - drug effects ; Neurons - cytology ; Neurons - drug effects ; Neurons - metabolism ; Organ Specificity - drug effects ; Phenotype ; RNA, Small Interfering - metabolism ; STEMCELL ; Transfusions. Complications. Transfusion reactions. 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We have engineered the PiggyBac transposable element to create an efficient system for gene delivery in hESCs. This redesigned system, named “ePiggyBac,” can deliver up to 18 Kb inserts, and transgene expression is observed in almost 90% of hES cells. ePiggyBac transposons can also carry insulators, inducible expression cassettes, and short hairpin RNAs for gain- and loss-of-function approaches. In hES cells, ePiggyBac's efficiency is superior to that of viral vectors and previously described transposons, including other PiggyBac-based systems. In addition, ePiggyBac transgenes can be removed from the hESC genome without leaving any mutation. We used this system to direct hESC differentiation toward a neuronal phenotype. We then removed the transposons to obtain transgene-free neuronal precursors and neurons. The ability to create fully reversible genetic modifications represents an important step toward clinical applications of hESCs.</description><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Applied cell therapy and gene therapy</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Lineage - drug effects</subject><subject>DNA Transposable Elements - genetics</subject><subject>Doxycycline - pharmacology</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Embryonic Stem Cells - drug effects</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene therapy</subject><subject>Gene Transfer Techniques</subject><subject>Genetic Engineering</subject><subject>Genome, Human - genetics</subject><subject>Health. Pharmaceutical industry</subject><subject>Humans</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Macaca</subject><subject>Medical sciences</subject><subject>Molecular Sequence Data</subject><subject>Mutagenesis, Insertional - drug effects</subject><subject>Neurons - cytology</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Organ Specificity - drug effects</subject><subject>Phenotype</subject><subject>RNA, Small Interfering - metabolism</subject><subject>STEMCELL</subject><subject>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><subject>Transgenes</subject><issn>1934-5909</issn><issn>1875-9777</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1vEzEQhi0Eom3gD3BAvsBtF3-s11jiUqWlRYqERMrZ8scYOdr1BntTKff-cLwkKjdOtkfPvDN6jNA7SlpKaP9p15YZxpYRoloiW0LpC3RJP0vRKCnly3pXvGuEIuoCXZWyI0RISuRrdEGV5Fx03SV6uk74NoToIqQZm-TxD3iEXKIdAD9kk8p-KmZ5bI_LNBymjO8gAb6BIVby-LdpExOYX9Bs9-BiTcM3MQTINTOaOU4Jx4TvD6Opw0abj1OqyHaJW8MwlDfoVTBDgbfnc4V-fr19WN83m-9339bXm8Z1Qs2NCoEqR4xknFlviLfcEym5lcFa5wNl3HvlWW9ILYpeVN4LzkzXSyuo4Sv08ZS7z9PvA5RZj7G4uoFJMB2KZtWOVDVmhdgJdHkqJUPQ-xxHk4-aEr241zu92NCLe02kru5r0_tz-sGO4P-1nGVX4MMZMMWZIVS7LpZnjtXxgvYL9-XEQXXxGCHrsnyPAx8zuFn7Kf5vjz98I6R5</recordid><startdate>20090904</startdate><enddate>20090904</enddate><creator>Lacoste, Arnaud</creator><creator>Berenshteyn, Frada</creator><creator>Brivanlou, Ali H.</creator><general>Elsevier Inc</general><general>Cell Press</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</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>7QO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20090904</creationdate><title>An Efficient and Reversible Transposable System for Gene Delivery and Lineage-Specific Differentiation in Human Embryonic Stem Cells</title><author>Lacoste, Arnaud ; Berenshteyn, Frada ; Brivanlou, Ali H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-9ff19c0a7232bda0db3d0773b7fbbcdf123dd9d26a073b565ff1d532a467b51a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Applied cell therapy and gene therapy</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Biotechnology</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Lineage - drug effects</topic><topic>DNA Transposable Elements - genetics</topic><topic>Doxycycline - pharmacology</topic><topic>Embryonic Stem Cells - cytology</topic><topic>Embryonic Stem Cells - drug effects</topic><topic>Embryonic Stem Cells - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene therapy</topic><topic>Gene Transfer Techniques</topic><topic>Genetic Engineering</topic><topic>Genome, Human - genetics</topic><topic>Health. Pharmaceutical industry</topic><topic>Humans</topic><topic>Industrial applications and implications. Economical aspects</topic><topic>Macaca</topic><topic>Medical sciences</topic><topic>Molecular Sequence Data</topic><topic>Mutagenesis, Insertional - drug effects</topic><topic>Neurons - cytology</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Organ Specificity - drug effects</topic><topic>Phenotype</topic><topic>RNA, Small Interfering - metabolism</topic><topic>STEMCELL</topic><topic>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</topic><topic>Transgenes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lacoste, Arnaud</creatorcontrib><creatorcontrib>Berenshteyn, Frada</creatorcontrib><creatorcontrib>Brivanlou, Ali H.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Cell stem cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lacoste, Arnaud</au><au>Berenshteyn, Frada</au><au>Brivanlou, Ali H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An Efficient and Reversible Transposable System for Gene Delivery and Lineage-Specific Differentiation in Human Embryonic Stem Cells</atitle><jtitle>Cell stem cell</jtitle><addtitle>Cell Stem Cell</addtitle><date>2009-09-04</date><risdate>2009</risdate><volume>5</volume><issue>3</issue><spage>332</spage><epage>342</epage><pages>332-342</pages><issn>1934-5909</issn><eissn>1875-9777</eissn><abstract>Unraveling the therapeutic potential of human embryonic stem cells (hESC) requires tools to modify their genome. We have engineered the PiggyBac transposable element to create an efficient system for gene delivery in hESCs. This redesigned system, named “ePiggyBac,” can deliver up to 18 Kb inserts, and transgene expression is observed in almost 90% of hES cells. ePiggyBac transposons can also carry insulators, inducible expression cassettes, and short hairpin RNAs for gain- and loss-of-function approaches. In hES cells, ePiggyBac's efficiency is superior to that of viral vectors and previously described transposons, including other PiggyBac-based systems. In addition, ePiggyBac transgenes can be removed from the hESC genome without leaving any mutation. We used this system to direct hESC differentiation toward a neuronal phenotype. We then removed the transposons to obtain transgene-free neuronal precursors and neurons. 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| ispartof | Cell stem cell, 2009-09, Vol.5 (3), p.332-342 |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete; Cell Press Free Archives; EZB-FREE-00999 freely available EZB journals |
| subjects | Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Applied cell therapy and gene therapy Base Sequence Biological and medical sciences Biotechnology Cell Differentiation - drug effects Cell Lineage - drug effects DNA Transposable Elements - genetics Doxycycline - pharmacology Embryonic Stem Cells - cytology Embryonic Stem Cells - drug effects Embryonic Stem Cells - metabolism Fundamental and applied biological sciences. Psychology Gene therapy Gene Transfer Techniques Genetic Engineering Genome, Human - genetics Health. Pharmaceutical industry Humans Industrial applications and implications. Economical aspects Macaca Medical sciences Molecular Sequence Data Mutagenesis, Insertional - drug effects Neurons - cytology Neurons - drug effects Neurons - metabolism Organ Specificity - drug effects Phenotype RNA, Small Interfering - metabolism STEMCELL Transfusions. Complications. Transfusion reactions. Cell and gene therapy Transgenes |
| title | An Efficient and Reversible Transposable System for Gene Delivery and Lineage-Specific Differentiation in Human Embryonic Stem Cells |
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