A red/far-red light-responsive bi-stable toggle switch to control gene expression in mammalian cells
Growth and differentiation of multicellular systems is orchestrated by spatially restricted gene expression programs in specialized subpopulations. The targeted manipulation of such processes by synthetic tools with high-spatiotemporal resolution could, therefore, enable a deepened understanding of...
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| Veröffentlicht in: | Nucleic acids research 2013-04, Vol.41 (7), p.e77-e77 |
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| creator | Müller, Konrad Engesser, Raphael Metzger, Stéphanie Schulz, Simon Kämpf, Michael M Busacker, Moritz Steinberg, Thorsten Tomakidi, Pascal Ehrbar, Martin Nagy, Ferenc Timmer, Jens Zubriggen, Matias D Weber, Wilfried |
| description | Growth and differentiation of multicellular systems is orchestrated by spatially restricted gene expression programs in specialized subpopulations. The targeted manipulation of such processes by synthetic tools with high-spatiotemporal resolution could, therefore, enable a deepened understanding of developmental processes and open new opportunities in tissue engineering. Here, we describe the first red/far-red light-triggered gene switch for mammalian cells for achieving gene expression control in time and space. We show that the system can reversibly be toggled between stable on- and off-states using short light pulses at 660 or 740 nm. Red light-induced gene expression was shown to correlate with the applied photon number and was compatible with different mammalian cell lines, including human primary cells. The light-induced expression kinetics were quantitatively analyzed by a mathematical model. We apply the system for the spatially controlled engineering of angiogenesis in chicken embryos. The system's performance combined with cell- and tissue-compatible regulating red light will enable unprecedented spatiotemporally controlled molecular interventions in mammalian cells, tissues and organisms. |
| doi_str_mv | 10.1093/nar/gkt002 |
| format | Article |
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The targeted manipulation of such processes by synthetic tools with high-spatiotemporal resolution could, therefore, enable a deepened understanding of developmental processes and open new opportunities in tissue engineering. Here, we describe the first red/far-red light-triggered gene switch for mammalian cells for achieving gene expression control in time and space. We show that the system can reversibly be toggled between stable on- and off-states using short light pulses at 660 or 740 nm. Red light-induced gene expression was shown to correlate with the applied photon number and was compatible with different mammalian cell lines, including human primary cells. The light-induced expression kinetics were quantitatively analyzed by a mathematical model. We apply the system for the spatially controlled engineering of angiogenesis in chicken embryos. The system's performance combined with cell- and tissue-compatible regulating red light will enable unprecedented spatiotemporally controlled molecular interventions in mammalian cells, tissues and organisms.</description><identifier>ISSN: 0305-1048</identifier><identifier>EISSN: 1362-4962</identifier><identifier>DOI: 10.1093/nar/gkt002</identifier><identifier>PMID: 23355611</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Animals ; Arabidopsis Proteins - genetics ; Arabidopsis Proteins - metabolism ; Basic Helix-Loop-Helix Transcription Factors - genetics ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; Cells, Cultured ; Chick Embryo ; Cricetinae ; Gene Expression Regulation - radiation effects ; Humans ; Light ; Methods Online ; Mice ; Neovascularization, Physiologic - genetics ; Neovascularization, Physiologic - radiation effects ; Phytochrome B - genetics ; Phytochrome B - metabolism ; Transgenes</subject><ispartof>Nucleic acids research, 2013-04, Vol.41 (7), p.e77-e77</ispartof><rights>The Author(s) 2013. 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The targeted manipulation of such processes by synthetic tools with high-spatiotemporal resolution could, therefore, enable a deepened understanding of developmental processes and open new opportunities in tissue engineering. Here, we describe the first red/far-red light-triggered gene switch for mammalian cells for achieving gene expression control in time and space. We show that the system can reversibly be toggled between stable on- and off-states using short light pulses at 660 or 740 nm. Red light-induced gene expression was shown to correlate with the applied photon number and was compatible with different mammalian cell lines, including human primary cells. The light-induced expression kinetics were quantitatively analyzed by a mathematical model. We apply the system for the spatially controlled engineering of angiogenesis in chicken embryos. The system's performance combined with cell- and tissue-compatible regulating red light will enable unprecedented spatiotemporally controlled molecular interventions in mammalian cells, tissues and organisms.</description><subject>Animals</subject><subject>Arabidopsis Proteins - genetics</subject><subject>Arabidopsis Proteins - metabolism</subject><subject>Basic Helix-Loop-Helix Transcription Factors - genetics</subject><subject>Basic Helix-Loop-Helix Transcription Factors - metabolism</subject><subject>Cells, Cultured</subject><subject>Chick Embryo</subject><subject>Cricetinae</subject><subject>Gene Expression Regulation - radiation effects</subject><subject>Humans</subject><subject>Light</subject><subject>Methods Online</subject><subject>Mice</subject><subject>Neovascularization, Physiologic - genetics</subject><subject>Neovascularization, Physiologic - radiation effects</subject><subject>Phytochrome B - genetics</subject><subject>Phytochrome B - metabolism</subject><subject>Transgenes</subject><issn>0305-1048</issn><issn>1362-4962</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkEtLxDAUhYMozji68QdI_kCdPJq03QjD4AsG3Oi6JOltG03T0sRR_70BH-jq3MvhfBwOQueUXFJS8bVX87p7iYSwA7SkXLIsryQ7REvCicgoycsFOgnhmRCaU5EfowXjXAhJ6RI1GzxDs27VnCXFznZ9TFeYRh_sHrC2WYhKO8Bx7Lok4c1G06cPm9HHeXS4Aw8Y3qeUCnb02Ho8qGFQziqPDTgXTtFRq1yAs29doaeb68ftXbZ7uL3fbnbZRCWPGZcFNLoltNVgSkqgpbpqeNUIJoGlvqUqpNamFKZgsiKNJHlb5bnRJS0rI_kKXX1xp1c9QGMgFVSunmY7qPmjHpWt_zve9nU37uu0WSEkS4CLv4Df5M9e_BNtIm-f</recordid><startdate>20130401</startdate><enddate>20130401</enddate><creator>Müller, Konrad</creator><creator>Engesser, Raphael</creator><creator>Metzger, Stéphanie</creator><creator>Schulz, Simon</creator><creator>Kämpf, Michael M</creator><creator>Busacker, Moritz</creator><creator>Steinberg, Thorsten</creator><creator>Tomakidi, Pascal</creator><creator>Ehrbar, Martin</creator><creator>Nagy, Ferenc</creator><creator>Timmer, Jens</creator><creator>Zubriggen, Matias D</creator><creator>Weber, Wilfried</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>5PM</scope></search><sort><creationdate>20130401</creationdate><title>A red/far-red light-responsive bi-stable toggle switch to control gene expression in mammalian cells</title><author>Müller, Konrad ; Engesser, Raphael ; Metzger, Stéphanie ; Schulz, Simon ; Kämpf, Michael M ; Busacker, Moritz ; Steinberg, Thorsten ; Tomakidi, Pascal ; Ehrbar, Martin ; Nagy, Ferenc ; Timmer, Jens ; Zubriggen, Matias D ; Weber, Wilfried</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p163t-367edbf01fbec810ef1b9d39d526e25618a76bbc85c72690d604f944cb8189c63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Arabidopsis Proteins - genetics</topic><topic>Arabidopsis Proteins - metabolism</topic><topic>Basic Helix-Loop-Helix Transcription Factors - genetics</topic><topic>Basic Helix-Loop-Helix Transcription Factors - metabolism</topic><topic>Cells, Cultured</topic><topic>Chick Embryo</topic><topic>Cricetinae</topic><topic>Gene Expression Regulation - radiation effects</topic><topic>Humans</topic><topic>Light</topic><topic>Methods Online</topic><topic>Mice</topic><topic>Neovascularization, Physiologic - genetics</topic><topic>Neovascularization, Physiologic - radiation effects</topic><topic>Phytochrome B - genetics</topic><topic>Phytochrome B - metabolism</topic><topic>Transgenes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Müller, Konrad</creatorcontrib><creatorcontrib>Engesser, Raphael</creatorcontrib><creatorcontrib>Metzger, Stéphanie</creatorcontrib><creatorcontrib>Schulz, Simon</creatorcontrib><creatorcontrib>Kämpf, Michael M</creatorcontrib><creatorcontrib>Busacker, Moritz</creatorcontrib><creatorcontrib>Steinberg, Thorsten</creatorcontrib><creatorcontrib>Tomakidi, Pascal</creatorcontrib><creatorcontrib>Ehrbar, Martin</creatorcontrib><creatorcontrib>Nagy, Ferenc</creatorcontrib><creatorcontrib>Timmer, Jens</creatorcontrib><creatorcontrib>Zubriggen, Matias D</creatorcontrib><creatorcontrib>Weber, Wilfried</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nucleic acids research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Müller, Konrad</au><au>Engesser, Raphael</au><au>Metzger, Stéphanie</au><au>Schulz, Simon</au><au>Kämpf, Michael M</au><au>Busacker, Moritz</au><au>Steinberg, Thorsten</au><au>Tomakidi, Pascal</au><au>Ehrbar, Martin</au><au>Nagy, Ferenc</au><au>Timmer, Jens</au><au>Zubriggen, Matias D</au><au>Weber, Wilfried</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A red/far-red light-responsive bi-stable toggle switch to control gene expression in mammalian cells</atitle><jtitle>Nucleic acids research</jtitle><addtitle>Nucleic Acids Res</addtitle><date>2013-04-01</date><risdate>2013</risdate><volume>41</volume><issue>7</issue><spage>e77</spage><epage>e77</epage><pages>e77-e77</pages><issn>0305-1048</issn><eissn>1362-4962</eissn><abstract>Growth and differentiation of multicellular systems is orchestrated by spatially restricted gene expression programs in specialized subpopulations. The targeted manipulation of such processes by synthetic tools with high-spatiotemporal resolution could, therefore, enable a deepened understanding of developmental processes and open new opportunities in tissue engineering. Here, we describe the first red/far-red light-triggered gene switch for mammalian cells for achieving gene expression control in time and space. We show that the system can reversibly be toggled between stable on- and off-states using short light pulses at 660 or 740 nm. Red light-induced gene expression was shown to correlate with the applied photon number and was compatible with different mammalian cell lines, including human primary cells. The light-induced expression kinetics were quantitatively analyzed by a mathematical model. We apply the system for the spatially controlled engineering of angiogenesis in chicken embryos. 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| subjects | Animals Arabidopsis Proteins - genetics Arabidopsis Proteins - metabolism Basic Helix-Loop-Helix Transcription Factors - genetics Basic Helix-Loop-Helix Transcription Factors - metabolism Cells, Cultured Chick Embryo Cricetinae Gene Expression Regulation - radiation effects Humans Light Methods Online Mice Neovascularization, Physiologic - genetics Neovascularization, Physiologic - radiation effects Phytochrome B - genetics Phytochrome B - metabolism Transgenes |
| title | A red/far-red light-responsive bi-stable toggle switch to control gene expression in mammalian cells |
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