MicroRNAs control the apoptotic threshold in primed pluripotent stem cells through regulation of BIM
Mammalian primed pluripotent stem cells have been shown to be highly susceptible to cell death stimuli due to their low apoptotic threshold, but how this threshold is regulated remains largely unknown. Here we identify microRNA (miRNA)-mediated regulation as a key mechanism controlling apoptosis in...
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| Veröffentlicht in: | Genes & development 2014-09, Vol.28 (17), p.1873-1878 |
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| container_title | Genes & development |
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| creator | Pernaute, Barbara Spruce, Thomas Smith, Kimberley M Sánchez-Nieto, Juan Miguel Manzanares, Miguel Cobb, Bradley Rodríguez, Tristan A |
| description | Mammalian primed pluripotent stem cells have been shown to be highly susceptible to cell death stimuli due to their low apoptotic threshold, but how this threshold is regulated remains largely unknown. Here we identify microRNA (miRNA)-mediated regulation as a key mechanism controlling apoptosis in the post-implantation epiblast. Moreover, we found that three miRNA families, miR-20, miR-92, and miR-302, control the mitochondrial apoptotic machinery by fine-tuning the levels of expression of the proapoptotic protein BIM. These families therefore represent an essential buffer needed to maintain cell survival in stem cells that are primed for not only differentiation but also cell death. |
| doi_str_mv | 10.1101/gad.245621.114 |
| format | Article |
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Here we identify microRNA (miRNA)-mediated regulation as a key mechanism controlling apoptosis in the post-implantation epiblast. Moreover, we found that three miRNA families, miR-20, miR-92, and miR-302, control the mitochondrial apoptotic machinery by fine-tuning the levels of expression of the proapoptotic protein BIM. 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These families therefore represent an essential buffer needed to maintain cell survival in stem cells that are primed for not only differentiation but also cell death.</description><subject>Animals</subject><subject>Apoptosis - genetics</subject><subject>Apoptosis Regulatory Proteins - genetics</subject><subject>Apoptosis Regulatory Proteins - metabolism</subject><subject>Bcl-2-Like Protein 11</subject><subject>Cell Survival - genetics</subject><subject>Cells, Cultured</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Mice</subject><subject>MicroRNAs - metabolism</subject><subject>Mitochondria - metabolism</subject><subject>Pluripotent Stem Cells - cytology</subject><subject>Pluripotent Stem Cells - metabolism</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Research Communication</subject><issn>0890-9369</issn><issn>1549-5477</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1r3DAQxUVpaTZprz0WHXvxRrI-bF0KScgXJC2U9iy00mhXxWs5khzIf1-ZTUN66ml4zOPxm3kIfaJkTSmhp1vj1i0XsqVV8zdoRQVXjeBd9xatSK9Io5hUR-g459-EEEmkfI-OWkF7LjuxQu4-2BR_fDvL2MaxpDjgsgNspjiVWIKtKkHexcHhMOIphT04PA1zClMsMBacC-yxhWHIizXO2x1OsJ0HU0IccfT4_Pb-A3rnzZDh4_M8Qb-uLn9e3DR3369vL87uGstbVpreAvOwkcpbr6ySlhNJrSB-o5xydUOg984B2zDTG0s9aZnjwoNzloBj7AR9PeRO86Zy2sqXzKAXapOedDRB_7sZw05v46PmVHWK8xrw5TkgxYcZctH7kJfjzAhxzppKSuurVd_-3yokEZ3qxYK1Pljrp3NO4F-IKNFLi7q2qA8tVr1gfH59x4v9b23sD0JknJs</recordid><startdate>20140901</startdate><enddate>20140901</enddate><creator>Pernaute, Barbara</creator><creator>Spruce, Thomas</creator><creator>Smith, Kimberley M</creator><creator>Sánchez-Nieto, Juan Miguel</creator><creator>Manzanares, Miguel</creator><creator>Cobb, Bradley</creator><creator>Rodríguez, Tristan A</creator><general>Cold Spring Harbor Laboratory Press</general><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>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20140901</creationdate><title>MicroRNAs control the apoptotic threshold in primed pluripotent stem cells through regulation of BIM</title><author>Pernaute, Barbara ; Spruce, Thomas ; Smith, Kimberley M ; Sánchez-Nieto, Juan Miguel ; Manzanares, Miguel ; Cobb, Bradley ; Rodríguez, Tristan A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c423t-8ce3feb69fcf9c96c4061c50fb9d9dfeb0e8fdde3b3a8ac1f023d45feddc0ed33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Apoptosis - genetics</topic><topic>Apoptosis Regulatory Proteins - genetics</topic><topic>Apoptosis Regulatory Proteins - metabolism</topic><topic>Bcl-2-Like Protein 11</topic><topic>Cell Survival - genetics</topic><topic>Cells, Cultured</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Mice</topic><topic>MicroRNAs - metabolism</topic><topic>Mitochondria - metabolism</topic><topic>Pluripotent Stem Cells - cytology</topic><topic>Pluripotent Stem Cells - metabolism</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Research Communication</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pernaute, Barbara</creatorcontrib><creatorcontrib>Spruce, Thomas</creatorcontrib><creatorcontrib>Smith, Kimberley M</creatorcontrib><creatorcontrib>Sánchez-Nieto, Juan Miguel</creatorcontrib><creatorcontrib>Manzanares, Miguel</creatorcontrib><creatorcontrib>Cobb, Bradley</creatorcontrib><creatorcontrib>Rodríguez, Tristan A</creatorcontrib><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>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genes & development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pernaute, Barbara</au><au>Spruce, Thomas</au><au>Smith, Kimberley M</au><au>Sánchez-Nieto, Juan Miguel</au><au>Manzanares, Miguel</au><au>Cobb, Bradley</au><au>Rodríguez, Tristan A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MicroRNAs control the apoptotic threshold in primed pluripotent stem cells through regulation of BIM</atitle><jtitle>Genes & development</jtitle><addtitle>Genes Dev</addtitle><date>2014-09-01</date><risdate>2014</risdate><volume>28</volume><issue>17</issue><spage>1873</spage><epage>1878</epage><pages>1873-1878</pages><issn>0890-9369</issn><eissn>1549-5477</eissn><abstract>Mammalian primed pluripotent stem cells have been shown to be highly susceptible to cell death stimuli due to their low apoptotic threshold, but how this threshold is regulated remains largely unknown. 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| subjects | Animals Apoptosis - genetics Apoptosis Regulatory Proteins - genetics Apoptosis Regulatory Proteins - metabolism Bcl-2-Like Protein 11 Cell Survival - genetics Cells, Cultured Gene Expression Profiling Gene Expression Regulation, Developmental Membrane Proteins - genetics Membrane Proteins - metabolism Mice MicroRNAs - metabolism Mitochondria - metabolism Pluripotent Stem Cells - cytology Pluripotent Stem Cells - metabolism Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins - metabolism Research Communication |
| title | MicroRNAs control the apoptotic threshold in primed pluripotent stem cells through regulation of BIM |
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