Generation of sensory hair cells by genetic programming with a combination of transcription factors
© 2015. Published by The Company of Biologists Ltd. Mechanosensory hair cells (HCs) are the primary receptors of our senses of hearing and balance. Elucidation of the transcriptional networks regulating HC fate determination and differentiation is crucial not only to understand inner ear development...
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| Veröffentlicht in: | Development (Cambridge) 2015-06, Vol.142 (11), p.1948-1959 |
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| container_end_page | 1959 |
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| container_issue | 11 |
| container_start_page | 1948 |
| container_title | Development (Cambridge) |
| container_volume | 142 |
| creator | Costa, Aida Sanchez-Guardado, Luis Juniat, Stephanie Gale, Jonathan E. Daudet, Nicolas Pinto Henrique, Domingos Manuel |
| description | © 2015. Published by The Company of Biologists Ltd.
Mechanosensory hair cells (HCs) are the primary receptors of our senses of hearing and balance. Elucidation of the transcriptional networks regulating HC fate determination and differentiation is crucial not only to understand inner ear development but also to improve cell replacement therapies for hearing disorders. Here, we show that combined expression of the transcription factors Gfi1, Pou4f3 and Atoh1 can induce direct programming towards HC fate, both during in vitro mouse embryonic stem cell differentiation and following ectopic expression in chick embryonic otic epithelium. Induced HCs (iHCs) express numerous HC-specific markers and exhibit polarized membrane protrusions reminiscent of stereociliary bundles. Transcriptome profiling confirms the progressive establishment of a HC-specific gene signature during in vitro iHC programming. Overall, this work provides a novel approach to achieve robust and highly efficient HC production in vitro, which could be used as a model to study HC development and to drive inner ear HC regeneration.
This work was supported by Fundação para a Ciência e Tecnologia, Portugal [PTDC/SAU-NEU/71310/2006, SFRH/BD/38461/2007 to A.C.]. A.C. was also a recipient of an EMBO Short-Term Fellowship during her stay at the UCL Ear Institute. S.J. is funded by a UCL Impact Studentship to J.E.G. Work in N.D.'s lab is supported by the BBSRC [BB/L003163/1]. |
| doi_str_mv | 10.1242/dev.119149 |
| format | Article |
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Mechanosensory hair cells (HCs) are the primary receptors of our senses of hearing and balance. Elucidation of the transcriptional networks regulating HC fate determination and differentiation is crucial not only to understand inner ear development but also to improve cell replacement therapies for hearing disorders. Here, we show that combined expression of the transcription factors Gfi1, Pou4f3 and Atoh1 can induce direct programming towards HC fate, both during in vitro mouse embryonic stem cell differentiation and following ectopic expression in chick embryonic otic epithelium. Induced HCs (iHCs) express numerous HC-specific markers and exhibit polarized membrane protrusions reminiscent of stereociliary bundles. Transcriptome profiling confirms the progressive establishment of a HC-specific gene signature during in vitro iHC programming. Overall, this work provides a novel approach to achieve robust and highly efficient HC production in vitro, which could be used as a model to study HC development and to drive inner ear HC regeneration.
This work was supported by Fundação para a Ciência e Tecnologia, Portugal [PTDC/SAU-NEU/71310/2006, SFRH/BD/38461/2007 to A.C.]. A.C. was also a recipient of an EMBO Short-Term Fellowship during her stay at the UCL Ear Institute. S.J. is funded by a UCL Impact Studentship to J.E.G. Work in N.D.'s lab is supported by the BBSRC [BB/L003163/1].</description><identifier>ISSN: 0950-1991</identifier><identifier>EISSN: 1477-9129</identifier><identifier>DOI: 10.1242/dev.119149</identifier><identifier>PMID: 26015538</identifier><language>eng</language><publisher>England: The Company of Biologists</publisher><subject>Animals ; Atoh1 ; Cell Differentiation - drug effects ; Cell Differentiation - genetics ; Cell Lineage - drug effects ; Cell Lineage - genetics ; Cell Shape - drug effects ; Cell type programming ; Cellular Reprogramming - drug effects ; Chick Embryo ; Embryonic Stem Cells - cytology ; Embryonic Stem Cells - drug effects ; Embryonic Stem Cells - metabolism ; Embryonic Stem Cells - ultrastructure ; Fluorescence ; Gene Expression Profiling ; Gene Expression Regulation, Developmental - drug effects ; Gene regulation ; Genes, Reporter ; Gfi1 ; Hair cells ; Hair Cells, Auditory - cytology ; Hair Cells, Auditory - drug effects ; Hair Cells, Auditory - metabolism ; Mice ; Receptors, Notch - metabolism ; Signal Transduction - drug effects ; Signal Transduction - genetics ; Transcription Factors - metabolism ; Transcriptome - genetics ; Tretinoin - pharmacology</subject><ispartof>Development (Cambridge), 2015-06, Vol.142 (11), p.1948-1959</ispartof><rights>2015. Published by The Company of Biologists Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c382t-b351edbddb8f2cfc4c98031bfb1c26ded5e2da06b3b725d3a88984c6c1ddcc3f3</citedby><cites>FETCH-LOGICAL-c382t-b351edbddb8f2cfc4c98031bfb1c26ded5e2da06b3b725d3a88984c6c1ddcc3f3</cites><orcidid>0000-0001-8869-1894 ; 0000-0002-5314-3895 ; 0000-0001-5598-8608</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3665,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26015538$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Costa, Aida</creatorcontrib><creatorcontrib>Sanchez-Guardado, Luis</creatorcontrib><creatorcontrib>Juniat, Stephanie</creatorcontrib><creatorcontrib>Gale, Jonathan E.</creatorcontrib><creatorcontrib>Daudet, Nicolas</creatorcontrib><creatorcontrib>Pinto Henrique, Domingos Manuel</creatorcontrib><title>Generation of sensory hair cells by genetic programming with a combination of transcription factors</title><title>Development (Cambridge)</title><addtitle>Development</addtitle><description>© 2015. Published by The Company of Biologists Ltd.
Mechanosensory hair cells (HCs) are the primary receptors of our senses of hearing and balance. Elucidation of the transcriptional networks regulating HC fate determination and differentiation is crucial not only to understand inner ear development but also to improve cell replacement therapies for hearing disorders. Here, we show that combined expression of the transcription factors Gfi1, Pou4f3 and Atoh1 can induce direct programming towards HC fate, both during in vitro mouse embryonic stem cell differentiation and following ectopic expression in chick embryonic otic epithelium. Induced HCs (iHCs) express numerous HC-specific markers and exhibit polarized membrane protrusions reminiscent of stereociliary bundles. Transcriptome profiling confirms the progressive establishment of a HC-specific gene signature during in vitro iHC programming. Overall, this work provides a novel approach to achieve robust and highly efficient HC production in vitro, which could be used as a model to study HC development and to drive inner ear HC regeneration.
This work was supported by Fundação para a Ciência e Tecnologia, Portugal [PTDC/SAU-NEU/71310/2006, SFRH/BD/38461/2007 to A.C.]. A.C. was also a recipient of an EMBO Short-Term Fellowship during her stay at the UCL Ear Institute. S.J. is funded by a UCL Impact Studentship to J.E.G. Work in N.D.'s lab is supported by the BBSRC [BB/L003163/1].</description><subject>Animals</subject><subject>Atoh1</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Lineage - drug effects</subject><subject>Cell Lineage - genetics</subject><subject>Cell Shape - drug effects</subject><subject>Cell type programming</subject><subject>Cellular Reprogramming - drug effects</subject><subject>Chick Embryo</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Embryonic Stem Cells - drug effects</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>Embryonic Stem Cells - ultrastructure</subject><subject>Fluorescence</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Developmental - drug effects</subject><subject>Gene regulation</subject><subject>Genes, Reporter</subject><subject>Gfi1</subject><subject>Hair cells</subject><subject>Hair Cells, Auditory - cytology</subject><subject>Hair Cells, Auditory - drug effects</subject><subject>Hair Cells, Auditory - metabolism</subject><subject>Mice</subject><subject>Receptors, Notch - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Transcriptome - genetics</subject><subject>Tretinoin - pharmacology</subject><issn>0950-1991</issn><issn>1477-9129</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMFKxDAQhoMouq5efACJNxG6ZpKmTY4iugqCFz2HZJKukW27Jl1l397qqldPA8M3_8x8hJwAmwEv-aUP7zMADaXeIRMo67rQwPUumTAtWQFawwE5zPmVMSaqut4nB7xiIKVQE4Lz0IVkh9h3tG9oDl3u04a-2JgohuUyU7ehi5EZItJV6hfJtm3sFvQjDi_UUuxbF7u_-SHZLmOKq-9GY3HoUz4ie41d5nD8U6fk-fbm6fqueHic319fPRQoFB8KJyQE77x3quHYYIlaMQGucYC88sHLwL1llROu5tILq5RWJVYI3iOKRkzJ-TZ3vPNtHfJg2pi_nrBd6NfZgGKq0qMD_j9aKVHLsgIxohdbFFOfcwqNWaXY2rQxwMyXfzP6N1v_I3z6k7t2bfB_6K_wETjbAgmtXZkU3mMe7LiQlRKMFEJz8QmccY2f</recordid><startdate>20150601</startdate><enddate>20150601</enddate><creator>Costa, Aida</creator><creator>Sanchez-Guardado, Luis</creator><creator>Juniat, Stephanie</creator><creator>Gale, Jonathan E.</creator><creator>Daudet, Nicolas</creator><creator>Pinto Henrique, Domingos Manuel</creator><general>The Company of Biologists</general><scope>RCLKO</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>7X8</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><orcidid>https://orcid.org/0000-0001-8869-1894</orcidid><orcidid>https://orcid.org/0000-0002-5314-3895</orcidid><orcidid>https://orcid.org/0000-0001-5598-8608</orcidid></search><sort><creationdate>20150601</creationdate><title>Generation of sensory hair cells by genetic programming with a combination of transcription factors</title><author>Costa, Aida ; Sanchez-Guardado, Luis ; Juniat, Stephanie ; Gale, Jonathan E. ; Daudet, Nicolas ; Pinto Henrique, Domingos Manuel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c382t-b351edbddb8f2cfc4c98031bfb1c26ded5e2da06b3b725d3a88984c6c1ddcc3f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Atoh1</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Lineage - drug effects</topic><topic>Cell Lineage - genetics</topic><topic>Cell Shape - drug effects</topic><topic>Cell type programming</topic><topic>Cellular Reprogramming - drug effects</topic><topic>Chick Embryo</topic><topic>Embryonic Stem Cells - cytology</topic><topic>Embryonic Stem Cells - drug effects</topic><topic>Embryonic Stem Cells - metabolism</topic><topic>Embryonic Stem Cells - ultrastructure</topic><topic>Fluorescence</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Developmental - drug effects</topic><topic>Gene regulation</topic><topic>Genes, Reporter</topic><topic>Gfi1</topic><topic>Hair cells</topic><topic>Hair Cells, Auditory - cytology</topic><topic>Hair Cells, Auditory - drug effects</topic><topic>Hair Cells, Auditory - metabolism</topic><topic>Mice</topic><topic>Receptors, Notch - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Transcriptome - genetics</topic><topic>Tretinoin - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Costa, Aida</creatorcontrib><creatorcontrib>Sanchez-Guardado, Luis</creatorcontrib><creatorcontrib>Juniat, Stephanie</creatorcontrib><creatorcontrib>Gale, Jonathan E.</creatorcontrib><creatorcontrib>Daudet, Nicolas</creatorcontrib><creatorcontrib>Pinto Henrique, Domingos Manuel</creatorcontrib><collection>RCAAP open access repository</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Development (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Costa, Aida</au><au>Sanchez-Guardado, Luis</au><au>Juniat, Stephanie</au><au>Gale, Jonathan E.</au><au>Daudet, Nicolas</au><au>Pinto Henrique, Domingos Manuel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Generation of sensory hair cells by genetic programming with a combination of transcription factors</atitle><jtitle>Development (Cambridge)</jtitle><addtitle>Development</addtitle><date>2015-06-01</date><risdate>2015</risdate><volume>142</volume><issue>11</issue><spage>1948</spage><epage>1959</epage><pages>1948-1959</pages><issn>0950-1991</issn><eissn>1477-9129</eissn><abstract>© 2015. Published by The Company of Biologists Ltd.
Mechanosensory hair cells (HCs) are the primary receptors of our senses of hearing and balance. Elucidation of the transcriptional networks regulating HC fate determination and differentiation is crucial not only to understand inner ear development but also to improve cell replacement therapies for hearing disorders. Here, we show that combined expression of the transcription factors Gfi1, Pou4f3 and Atoh1 can induce direct programming towards HC fate, both during in vitro mouse embryonic stem cell differentiation and following ectopic expression in chick embryonic otic epithelium. Induced HCs (iHCs) express numerous HC-specific markers and exhibit polarized membrane protrusions reminiscent of stereociliary bundles. Transcriptome profiling confirms the progressive establishment of a HC-specific gene signature during in vitro iHC programming. Overall, this work provides a novel approach to achieve robust and highly efficient HC production in vitro, which could be used as a model to study HC development and to drive inner ear HC regeneration.
This work was supported by Fundação para a Ciência e Tecnologia, Portugal [PTDC/SAU-NEU/71310/2006, SFRH/BD/38461/2007 to A.C.]. A.C. was also a recipient of an EMBO Short-Term Fellowship during her stay at the UCL Ear Institute. S.J. is funded by a UCL Impact Studentship to J.E.G. Work in N.D.'s lab is supported by the BBSRC [BB/L003163/1].</abstract><cop>England</cop><pub>The Company of Biologists</pub><pmid>26015538</pmid><doi>10.1242/dev.119149</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-8869-1894</orcidid><orcidid>https://orcid.org/0000-0002-5314-3895</orcidid><orcidid>https://orcid.org/0000-0001-5598-8608</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0950-1991 |
| ispartof | Development (Cambridge), 2015-06, Vol.142 (11), p.1948-1959 |
| issn | 0950-1991 1477-9129 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1808690362 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection; Company of Biologists |
| subjects | Animals Atoh1 Cell Differentiation - drug effects Cell Differentiation - genetics Cell Lineage - drug effects Cell Lineage - genetics Cell Shape - drug effects Cell type programming Cellular Reprogramming - drug effects Chick Embryo Embryonic Stem Cells - cytology Embryonic Stem Cells - drug effects Embryonic Stem Cells - metabolism Embryonic Stem Cells - ultrastructure Fluorescence Gene Expression Profiling Gene Expression Regulation, Developmental - drug effects Gene regulation Genes, Reporter Gfi1 Hair cells Hair Cells, Auditory - cytology Hair Cells, Auditory - drug effects Hair Cells, Auditory - metabolism Mice Receptors, Notch - metabolism Signal Transduction - drug effects Signal Transduction - genetics Transcription Factors - metabolism Transcriptome - genetics Tretinoin - pharmacology |
| title | Generation of sensory hair cells by genetic programming with a combination of transcription factors |
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