MicroRNA‐134 Modulates the Differentiation of Mouse Embryonic Stem Cells, Where It Causes Post‐Transcriptional Attenuation of Nanog and LRH1
Hundreds of microRNAs (miRNAs) are expressed in mammalian cells, where they aid in modulating gene expression by mediating mRNA transcript cleavage and/or regulation of translation rate. Functional studies to date have demonstrated that several of these miRNAs are important during development. Howev...
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creator | Tay, Yvonne M.‐S. Tam, Wai‐Leong Ang, Yen‐Sin Gaughwin, Philip M. Yang, Henry Wang, Weijia Liu, Rubing George, Joshy Ng, Huck‐Hui Perera, Ranjan J. Lufkin, Thomas Rigoutsos, Isidore Thomson, Andrew M. Lim, Bing |
description | Hundreds of microRNAs (miRNAs) are expressed in mammalian cells, where they aid in modulating gene expression by mediating mRNA transcript cleavage and/or regulation of translation rate. Functional studies to date have demonstrated that several of these miRNAs are important during development. However, the role of miRNAs in the regulation of stem cell growth and differentiation is not well understood. We show herein that microRNA (miR)‐134 levels are maximally elevated at day 4 after retinoic acid‐induced differentiation or day 2 after N2B27‐induced differentiation of mouse embryonic stem cells (mESCs), but this change is not observed during embryoid body differentiation. The elevation of miR‐134 levels alone in mESCs enhances differentiation toward ectodermal lineages, an effect that is blocked by a miR‐134 antagonist. The promotion of mESC differentiation by miR‐134 is due, in part, to its direct translational attenuation of Nanog and LRH1, both of which are known positive regulators of Oct4/POU5F1 and mESC growth. Together, the data demonstrate that miR‐134 alone can enhance the differentiation of mESCs to ectodermal lineages and establish a functional role for miR‐134 in modulating mESC differentiation through its potential to target and regulate multiple mRNAs.
Disclosure of potential conflicts of interest is found at the end of this article. |
doi_str_mv | 10.1634/stemcells.2007-0295 |
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Disclosure of potential conflicts of interest is found at the end of this article.</description><subject>Animals</subject><subject>Blotting, Northern</subject><subject>Blotting, Western</subject><subject>Cell differentiation</subject><subject>Cell Differentiation - genetics</subject><subject>Cells, Cultured</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Embryonic stem cells</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Fluorescent Antibody Technique</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Genetic Vectors</subject><subject>Homeodomain Proteins - metabolism</subject><subject>In Situ Hybridization</subject><subject>Mice</subject><subject>MicroRNAs</subject><subject>MicroRNAs - metabolism</subject><subject>Nanog Homeobox Protein</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Receptors, Cytoplasmic and Nuclear - metabolism</subject><subject>Retinoic acid</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Transcription, Genetic</subject><subject>Transfection</subject><issn>1066-5099</issn><issn>1549-4918</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkctuEzEUhi1ERS_wBEjIK1ZM8X3GYhWFlFZKCmojsbSc8RlqNJfU9qjKro_QZ-RJ8ChRWZaVz-I7v36fD6H3lJxTxcXnmKCroW3jOSOkLAjT8hU6oVLoQmhavc4zUaqQROtjdBrjb0KokFX1Bh3TUlNVEXGCnla-DsPN9ezP4xPlAq8GN7Y2QcTpDvBX3zQQoE_eJj_0eGgyMEbAi24TdkPva3ybW-D5VOMT_nmXYXyV8NxmKOIfQ0w5dx1sH-vgt1OGbfEsJejH58Rr2w-_sO0dXt5c0rfoqLFthHeH9wytLxbr-WWx_P7taj5bFrXgtCys3ghV5nYOiNDSUqqhEY5ILQhUupFc8EowyjTIjZPKMWWd45Q0krJG8zP0cR-7DcP9CDGZzsfpmraH_ENTEka4EuRFkGqhOCt5BvkezPeMMUBjtsF3NuwMJWYSZp6FmUmYmYTlrQ-H-HHTgfu3czCUgS974MG3sPufTHO7XqyYyrZL_hccyqkI</recordid><startdate>200801</startdate><enddate>200801</enddate><creator>Tay, Yvonne M.‐S.</creator><creator>Tam, Wai‐Leong</creator><creator>Ang, Yen‐Sin</creator><creator>Gaughwin, Philip M.</creator><creator>Yang, Henry</creator><creator>Wang, Weijia</creator><creator>Liu, Rubing</creator><creator>George, Joshy</creator><creator>Ng, Huck‐Hui</creator><creator>Perera, Ranjan J.</creator><creator>Lufkin, Thomas</creator><creator>Rigoutsos, Isidore</creator><creator>Thomson, Andrew M.</creator><creator>Lim, Bing</creator><general>John Wiley & Sons, Ltd</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>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>200801</creationdate><title>MicroRNA‐134 Modulates the Differentiation of Mouse Embryonic Stem Cells, Where It Causes Post‐Transcriptional Attenuation of Nanog and LRH1</title><author>Tay, Yvonne M.‐S. ; Tam, Wai‐Leong ; Ang, Yen‐Sin ; Gaughwin, Philip M. ; Yang, Henry ; Wang, Weijia ; Liu, Rubing ; George, Joshy ; Ng, Huck‐Hui ; Perera, Ranjan J. ; Lufkin, Thomas ; Rigoutsos, Isidore ; Thomson, Andrew M. ; Lim, Bing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4317-a9b467ffede0495a119ef4d05940e89f5343842129e5bd56d26add310f512f93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Blotting, Northern</topic><topic>Blotting, Western</topic><topic>Cell differentiation</topic><topic>Cell Differentiation - genetics</topic><topic>Cells, Cultured</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Embryonic stem cells</topic><topic>Embryonic Stem Cells - cytology</topic><topic>Fluorescent Antibody Technique</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Genetic Vectors</topic><topic>Homeodomain Proteins - metabolism</topic><topic>In Situ Hybridization</topic><topic>Mice</topic><topic>MicroRNAs</topic><topic>MicroRNAs - metabolism</topic><topic>Nanog Homeobox Protein</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Receptors, Cytoplasmic and Nuclear - metabolism</topic><topic>Retinoic acid</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Transcription, Genetic</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tay, Yvonne M.‐S.</creatorcontrib><creatorcontrib>Tam, Wai‐Leong</creatorcontrib><creatorcontrib>Ang, Yen‐Sin</creatorcontrib><creatorcontrib>Gaughwin, Philip M.</creatorcontrib><creatorcontrib>Yang, Henry</creatorcontrib><creatorcontrib>Wang, Weijia</creatorcontrib><creatorcontrib>Liu, Rubing</creatorcontrib><creatorcontrib>George, Joshy</creatorcontrib><creatorcontrib>Ng, Huck‐Hui</creatorcontrib><creatorcontrib>Perera, Ranjan J.</creatorcontrib><creatorcontrib>Lufkin, Thomas</creatorcontrib><creatorcontrib>Rigoutsos, Isidore</creatorcontrib><creatorcontrib>Thomson, Andrew M.</creatorcontrib><creatorcontrib>Lim, Bing</creatorcontrib><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>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>MEDLINE - Academic</collection><jtitle>Stem cells (Dayton, Ohio)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tay, Yvonne M.‐S.</au><au>Tam, Wai‐Leong</au><au>Ang, Yen‐Sin</au><au>Gaughwin, Philip M.</au><au>Yang, Henry</au><au>Wang, Weijia</au><au>Liu, Rubing</au><au>George, Joshy</au><au>Ng, Huck‐Hui</au><au>Perera, Ranjan J.</au><au>Lufkin, Thomas</au><au>Rigoutsos, Isidore</au><au>Thomson, Andrew M.</au><au>Lim, Bing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MicroRNA‐134 Modulates the Differentiation of Mouse Embryonic Stem Cells, Where It Causes Post‐Transcriptional Attenuation of Nanog and LRH1</atitle><jtitle>Stem cells (Dayton, Ohio)</jtitle><addtitle>Stem Cells</addtitle><date>2008-01</date><risdate>2008</risdate><volume>26</volume><issue>1</issue><spage>17</spage><epage>29</epage><pages>17-29</pages><issn>1066-5099</issn><eissn>1549-4918</eissn><abstract>Hundreds of microRNAs (miRNAs) are expressed in mammalian cells, where they aid in modulating gene expression by mediating mRNA transcript cleavage and/or regulation of translation rate. Functional studies to date have demonstrated that several of these miRNAs are important during development. However, the role of miRNAs in the regulation of stem cell growth and differentiation is not well understood. We show herein that microRNA (miR)‐134 levels are maximally elevated at day 4 after retinoic acid‐induced differentiation or day 2 after N2B27‐induced differentiation of mouse embryonic stem cells (mESCs), but this change is not observed during embryoid body differentiation. The elevation of miR‐134 levels alone in mESCs enhances differentiation toward ectodermal lineages, an effect that is blocked by a miR‐134 antagonist. The promotion of mESC differentiation by miR‐134 is due, in part, to its direct translational attenuation of Nanog and LRH1, both of which are known positive regulators of Oct4/POU5F1 and mESC growth. Together, the data demonstrate that miR‐134 alone can enhance the differentiation of mESCs to ectodermal lineages and establish a functional role for miR‐134 in modulating mESC differentiation through its potential to target and regulate multiple mRNAs.
Disclosure of potential conflicts of interest is found at the end of this article.</abstract><cop>Bristol</cop><pub>John Wiley & Sons, Ltd</pub><pmid>17916804</pmid><doi>10.1634/stemcells.2007-0295</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
subjects | Animals Blotting, Northern Blotting, Western Cell differentiation Cell Differentiation - genetics Cells, Cultured DNA-Binding Proteins - metabolism Embryonic stem cells Embryonic Stem Cells - cytology Fluorescent Antibody Technique Gene Expression Profiling Gene Expression Regulation, Developmental Genetic Vectors Homeodomain Proteins - metabolism In Situ Hybridization Mice MicroRNAs MicroRNAs - metabolism Nanog Homeobox Protein Oligonucleotide Array Sequence Analysis Receptors, Cytoplasmic and Nuclear - metabolism Retinoic acid Reverse Transcriptase Polymerase Chain Reaction Transcription, Genetic Transfection |
title | MicroRNA‐134 Modulates the Differentiation of Mouse Embryonic Stem Cells, Where It Causes Post‐Transcriptional Attenuation of Nanog and LRH1 |
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