MicroRNA expression patterns and function in endodermal differentiation of human embryonic stem cells
microRNAs (miRNAs) are small noncoding RNAs that regulate cognate mRNAs post-transcriptionally. Human embryonic stem cells (hESC), which exhibit the characteristics of pluripotency and self-renewal, may serve as a model to study the role of miRNAs in early human development. We aimed to determine wh...
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| Veröffentlicht in: | PloS one 2008-11, Vol.3 (11), p.e3726-e3726 |
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| creator | Tzur, Galit Levy, Asaf Meiri, Eti Barad, Omer Spector, Yael Bentwich, Zvi Mizrahi, Lina Katzenellenbogen, Mark Ben-Shushan, Etti Reubinoff, Benjamin E Galun, Eithan |
| description | microRNAs (miRNAs) are small noncoding RNAs that regulate cognate mRNAs post-transcriptionally. Human embryonic stem cells (hESC), which exhibit the characteristics of pluripotency and self-renewal, may serve as a model to study the role of miRNAs in early human development. We aimed to determine whether endodermally-differentiated hESC demonstrate a unique miRNA expression pattern, and whether overexpression of endoderm-specific miRNA may affect hESC differentiation.
miRNA expression was profiled in undifferentiated and NaButyrate-induced differentiated hESC of two lines, using microarray and quantitative RT-PCR. Then, the effect of lentiviral-based overexpression of liver-specific miR-122 on hESC differentiation was analyzed, using genomewide gene microarrays.
The miRNA profiling revealed expression of three novel miRNAs in undifferentiated and differentiated hESC. Upon NaButyrate induction, two of the most upregulated miRNAs common to both cell lines were miR-24 and miR-10a, whose target genes have been shown to inhibit endodermal differentiation. Furthermore, induction of several liver-enriched miRNAs, including miR-122 and miR-192, was observed in parallel to induction of endodermal gene expression. Stable overexpression of miR-122 in hESC was unable to direct spontaneous differentiation towards a clear endodermal fate, but rather, delayed general differentiation of these cells.
Our results demonstrate that expression of specific miRNAs correlates with that of specific genes upon differentiation, and highlight the potential role of miRNAs in endodermal differentiation of hESC. |
| doi_str_mv | 10.1371/journal.pone.0003726 |
| format | Article |
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miRNA expression was profiled in undifferentiated and NaButyrate-induced differentiated hESC of two lines, using microarray and quantitative RT-PCR. Then, the effect of lentiviral-based overexpression of liver-specific miR-122 on hESC differentiation was analyzed, using genomewide gene microarrays.
The miRNA profiling revealed expression of three novel miRNAs in undifferentiated and differentiated hESC. Upon NaButyrate induction, two of the most upregulated miRNAs common to both cell lines were miR-24 and miR-10a, whose target genes have been shown to inhibit endodermal differentiation. Furthermore, induction of several liver-enriched miRNAs, including miR-122 and miR-192, was observed in parallel to induction of endodermal gene expression. Stable overexpression of miR-122 in hESC was unable to direct spontaneous differentiation towards a clear endodermal fate, but rather, delayed general differentiation of these cells.
Our results demonstrate that expression of specific miRNAs correlates with that of specific genes upon differentiation, and highlight the potential role of miRNAs in endodermal differentiation of hESC.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0003726</identifier><identifier>PMID: 19015728</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Algorithms ; Analysis ; Cell Differentiation ; Cell Line ; Cell lines ; Cell self-renewal ; Cloning ; Differentiation ; DNA microarrays ; Embryo cells ; Embryonic stem cells ; Embryonic Stem Cells - cytology ; Embryos ; Endoderm ; Endoderm - metabolism ; Experiments ; Flow Cytometry ; Gastroenterology and Hepatology ; Gastroenterology and Hepatology/Hepatology ; Gene expression ; Gene Expression Profiling ; Gene therapy ; Genes ; Genetic Vectors ; Genetics and Genomics/Gene Therapy ; Genome, Human ; Genomes ; Genomics ; Humans ; Liver ; Metabolism ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; miRNA ; Morphogenesis ; Oligonucleotide Array Sequence Analysis ; Pluripotency ; Polymerase chain reaction ; Post-transcription ; Reverse Transcriptase Polymerase Chain Reaction ; Ribonucleic acid ; RNA ; RNA polymerase ; Signal transduction ; Sodium Oxybate - pharmacology ; Stem cells ; Transcription ; Transcription (Genetics) ; Transcription Factors - metabolism</subject><ispartof>PloS one, 2008-11, Vol.3 (11), p.e3726-e3726</ispartof><rights>COPYRIGHT 2008 Public Library of Science</rights><rights>2008 Tzur et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Tzur et al. 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c728t-b434d7352afd32fef8c21da625a985d46494b9738ba254f1e2f8f921540619d13</citedby><cites>FETCH-LOGICAL-c728t-b434d7352afd32fef8c21da625a985d46494b9738ba254f1e2f8f921540619d13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2581805/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2581805/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53770,53772,79347,79348</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19015728$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Lewin, Alfred</contributor><creatorcontrib>Tzur, Galit</creatorcontrib><creatorcontrib>Levy, Asaf</creatorcontrib><creatorcontrib>Meiri, Eti</creatorcontrib><creatorcontrib>Barad, Omer</creatorcontrib><creatorcontrib>Spector, Yael</creatorcontrib><creatorcontrib>Bentwich, Zvi</creatorcontrib><creatorcontrib>Mizrahi, Lina</creatorcontrib><creatorcontrib>Katzenellenbogen, Mark</creatorcontrib><creatorcontrib>Ben-Shushan, Etti</creatorcontrib><creatorcontrib>Reubinoff, Benjamin E</creatorcontrib><creatorcontrib>Galun, Eithan</creatorcontrib><title>MicroRNA expression patterns and function in endodermal differentiation of human embryonic stem cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>microRNAs (miRNAs) are small noncoding RNAs that regulate cognate mRNAs post-transcriptionally. Human embryonic stem cells (hESC), which exhibit the characteristics of pluripotency and self-renewal, may serve as a model to study the role of miRNAs in early human development. We aimed to determine whether endodermally-differentiated hESC demonstrate a unique miRNA expression pattern, and whether overexpression of endoderm-specific miRNA may affect hESC differentiation.
miRNA expression was profiled in undifferentiated and NaButyrate-induced differentiated hESC of two lines, using microarray and quantitative RT-PCR. Then, the effect of lentiviral-based overexpression of liver-specific miR-122 on hESC differentiation was analyzed, using genomewide gene microarrays.
The miRNA profiling revealed expression of three novel miRNAs in undifferentiated and differentiated hESC. Upon NaButyrate induction, two of the most upregulated miRNAs common to both cell lines were miR-24 and miR-10a, whose target genes have been shown to inhibit endodermal differentiation. Furthermore, induction of several liver-enriched miRNAs, including miR-122 and miR-192, was observed in parallel to induction of endodermal gene expression. Stable overexpression of miR-122 in hESC was unable to direct spontaneous differentiation towards a clear endodermal fate, but rather, delayed general differentiation of these cells.
Our results demonstrate that expression of specific miRNAs correlates with that of specific genes upon differentiation, and highlight the potential role of miRNAs in endodermal differentiation of hESC.</description><subject>Algorithms</subject><subject>Analysis</subject><subject>Cell Differentiation</subject><subject>Cell Line</subject><subject>Cell lines</subject><subject>Cell self-renewal</subject><subject>Cloning</subject><subject>Differentiation</subject><subject>DNA microarrays</subject><subject>Embryo cells</subject><subject>Embryonic stem cells</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Embryos</subject><subject>Endoderm</subject><subject>Endoderm - metabolism</subject><subject>Experiments</subject><subject>Flow Cytometry</subject><subject>Gastroenterology and Hepatology</subject><subject>Gastroenterology and Hepatology/Hepatology</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene therapy</subject><subject>Genes</subject><subject>Genetic Vectors</subject><subject>Genetics and Genomics/Gene Therapy</subject><subject>Genome, Human</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Humans</subject><subject>Liver</subject><subject>Metabolism</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>miRNA</subject><subject>Morphogenesis</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Pluripotency</subject><subject>Polymerase chain reaction</subject><subject>Post-transcription</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA polymerase</subject><subject>Signal transduction</subject><subject>Sodium Oxybate - pharmacology</subject><subject>Stem cells</subject><subject>Transcription</subject><subject>Transcription (Genetics)</subject><subject>Transcription Factors - metabolism</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl1rFDEUhgdRbF39B6IDQsGLXfM1M8mNsBQ_FqqF-nEbMsnJbspMsk1mpP33Zruj7ooXkouEc55zkvPmLYrnGC0wbfCb6zBGr7rFNnhYIIRoQ-oHxSkWlMxrgujDg_NJ8SSla4Qqyuv6cXGCBcJVQ_hpAZ-cjuHq87KE222ElFzw5VYNA0SfSuVNaUevh13U-RK8CQZir7rSOGshgh-cus8GW27GXmWmb-Nd8E6XaYC-1NB16WnxyKouwbNpnxXf3r_7ev5xfnH5YXW-vJjr_Jhh3jLKTEMroqyhxILlmmCjalIpwSvDaiZYKxrKW0UqZjEQy60guGKoxsJgOite7vtuu5DkpFCSmGLCqGANy8RqT5igruU2ul7FOxmUk_eBENdSxcHpDiQGwQwFbYmlTLSs5VqLtiGIKGGgqXOvt9NtY9uD0VmMqLqjpscZ7zZyHX5IUnHM82fMirOpQQw3I6RB9i7tBFMewphkLTiirOEZfPUX-O_ZFntqrfLznbch36rzMtA7nW1iXY4vWUOqijNKcsHro4LMDHA7rNWYklx9ufp_9vL7MXt2wG5AdcMmhW7cGSUdg2wPZg-mFMH-Fg8juXP5rznlzuVycnkue3Eo_J-iydb0JyAD-XE</recordid><startdate>20081118</startdate><enddate>20081118</enddate><creator>Tzur, Galit</creator><creator>Levy, Asaf</creator><creator>Meiri, Eti</creator><creator>Barad, Omer</creator><creator>Spector, Yael</creator><creator>Bentwich, Zvi</creator><creator>Mizrahi, Lina</creator><creator>Katzenellenbogen, Mark</creator><creator>Ben-Shushan, Etti</creator><creator>Reubinoff, Benjamin E</creator><creator>Galun, Eithan</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20081118</creationdate><title>MicroRNA expression patterns and function in endodermal differentiation of human embryonic stem cells</title><author>Tzur, Galit ; Levy, Asaf ; Meiri, Eti ; Barad, Omer ; Spector, Yael ; Bentwich, Zvi ; Mizrahi, Lina ; Katzenellenbogen, Mark ; Ben-Shushan, Etti ; Reubinoff, Benjamin E ; Galun, Eithan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c728t-b434d7352afd32fef8c21da625a985d46494b9738ba254f1e2f8f921540619d13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Algorithms</topic><topic>Analysis</topic><topic>Cell Differentiation</topic><topic>Cell Line</topic><topic>Cell lines</topic><topic>Cell self-renewal</topic><topic>Cloning</topic><topic>Differentiation</topic><topic>DNA microarrays</topic><topic>Embryo cells</topic><topic>Embryonic stem cells</topic><topic>Embryonic Stem Cells - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tzur, Galit</au><au>Levy, Asaf</au><au>Meiri, Eti</au><au>Barad, Omer</au><au>Spector, Yael</au><au>Bentwich, Zvi</au><au>Mizrahi, Lina</au><au>Katzenellenbogen, Mark</au><au>Ben-Shushan, Etti</au><au>Reubinoff, Benjamin E</au><au>Galun, Eithan</au><au>Lewin, Alfred</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MicroRNA expression patterns and function in endodermal differentiation of human embryonic stem cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2008-11-18</date><risdate>2008</risdate><volume>3</volume><issue>11</issue><spage>e3726</spage><epage>e3726</epage><pages>e3726-e3726</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>microRNAs (miRNAs) are small noncoding RNAs that regulate cognate mRNAs post-transcriptionally. Human embryonic stem cells (hESC), which exhibit the characteristics of pluripotency and self-renewal, may serve as a model to study the role of miRNAs in early human development. We aimed to determine whether endodermally-differentiated hESC demonstrate a unique miRNA expression pattern, and whether overexpression of endoderm-specific miRNA may affect hESC differentiation.
miRNA expression was profiled in undifferentiated and NaButyrate-induced differentiated hESC of two lines, using microarray and quantitative RT-PCR. Then, the effect of lentiviral-based overexpression of liver-specific miR-122 on hESC differentiation was analyzed, using genomewide gene microarrays.
The miRNA profiling revealed expression of three novel miRNAs in undifferentiated and differentiated hESC. Upon NaButyrate induction, two of the most upregulated miRNAs common to both cell lines were miR-24 and miR-10a, whose target genes have been shown to inhibit endodermal differentiation. Furthermore, induction of several liver-enriched miRNAs, including miR-122 and miR-192, was observed in parallel to induction of endodermal gene expression. Stable overexpression of miR-122 in hESC was unable to direct spontaneous differentiation towards a clear endodermal fate, but rather, delayed general differentiation of these cells.
Our results demonstrate that expression of specific miRNAs correlates with that of specific genes upon differentiation, and highlight the potential role of miRNAs in endodermal differentiation of hESC.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>19015728</pmid><doi>10.1371/journal.pone.0003726</doi><tpages>e3726</tpages><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1312439474 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; Full-Text Journals in Chemistry (Open access); EZB-FREE-00999 freely available EZB journals; PubMed Central; Directory of Open Access Journals |
| subjects | Algorithms Analysis Cell Differentiation Cell Line Cell lines Cell self-renewal Cloning Differentiation DNA microarrays Embryo cells Embryonic stem cells Embryonic Stem Cells - cytology Embryos Endoderm Endoderm - metabolism Experiments Flow Cytometry Gastroenterology and Hepatology Gastroenterology and Hepatology/Hepatology Gene expression Gene Expression Profiling Gene therapy Genes Genetic Vectors Genetics and Genomics/Gene Therapy Genome, Human Genomes Genomics Humans Liver Metabolism MicroRNA MicroRNAs MicroRNAs - genetics miRNA Morphogenesis Oligonucleotide Array Sequence Analysis Pluripotency Polymerase chain reaction Post-transcription Reverse Transcriptase Polymerase Chain Reaction Ribonucleic acid RNA RNA polymerase Signal transduction Sodium Oxybate - pharmacology Stem cells Transcription Transcription (Genetics) Transcription Factors - metabolism |
| title | MicroRNA expression patterns and function in endodermal differentiation of human embryonic stem cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-22T19%3A13%3A03IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=MicroRNA%20expression%20patterns%20and%20function%20in%20endodermal%20differentiation%20of%20human%20embryonic%20stem%20cells&rft.jtitle=PloS%20one&rft.au=Tzur,%20Galit&rft.date=2008-11-18&rft.volume=3&rft.issue=11&rft.spage=e3726&rft.epage=e3726&rft.pages=e3726-e3726&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0003726&rft_dat=%3Cgale_plos_%3EA472558432%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1312439474&rft_id=info:pmid/19015728&rft_galeid=A472558432&rft_doaj_id=oai_doaj_org_article_1e94d3ecf2f349b4b8cc9b7202a9de76&rfr_iscdi=true |