Functional analysis of Tcl1 using Tcl1-deficient mouse embryonic stem cells
Tcl1 is highly expressed in embryonic stem (ES) cells, but its expression rapidly decreases following differentiation. To assess Tcl1's roles in ES cells, we generated Tcl1-deficient and -overexpressing mouse ES cell lines. We found that Tcl1 was neither essential nor sufficient for maintaining...
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| creator | Miyazaki, Tatsushi Miyazaki, Satsuki Ashida, Masafumi Tanaka, Tomofumi Tashiro, Fumi Miyazaki, Jun-ichi |
| description | Tcl1 is highly expressed in embryonic stem (ES) cells, but its expression rapidly decreases following differentiation. To assess Tcl1's roles in ES cells, we generated Tcl1-deficient and -overexpressing mouse ES cell lines. We found that Tcl1 was neither essential nor sufficient for maintaining the undifferentiated state. Tcl1 is reported to activate Akt and to enhance cell proliferation. We found that Tcl1 expression levels correlated positively with the proliferation rate and negatively with the apoptosis of ES cells, but did not affect Akt phosphorylation. On the other hand, the phosphorylation level of β-catenin decreased in response to Tcl1 overexpression. We measured the β-catenin activity using the TOPflash reporter assay, and found that wild-type ES cells had low activity, which Tcl1 overexpression enhanced 1.8-fold. When the canonical Wnt signaling is activated by β-catenin stabilization, it reportedly helps maintain ES cells in the undifferentiated state. We then performed DNA microarray analyses between the Tcl1-deficient and -expressing ES cells. The results revealed that Tcl1 expression downregulated a distinct group of genes, including Ndp52, whose expression is very high in blastocysts but reduced in the primitive ectoderm. Based on these results, we discuss the possible roles of Tcl1 in ES cells. |
| doi_str_mv | 10.1371/journal.pone.0071645 |
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To assess Tcl1's roles in ES cells, we generated Tcl1-deficient and -overexpressing mouse ES cell lines. We found that Tcl1 was neither essential nor sufficient for maintaining the undifferentiated state. Tcl1 is reported to activate Akt and to enhance cell proliferation. We found that Tcl1 expression levels correlated positively with the proliferation rate and negatively with the apoptosis of ES cells, but did not affect Akt phosphorylation. On the other hand, the phosphorylation level of β-catenin decreased in response to Tcl1 overexpression. We measured the β-catenin activity using the TOPflash reporter assay, and found that wild-type ES cells had low activity, which Tcl1 overexpression enhanced 1.8-fold. When the canonical Wnt signaling is activated by β-catenin stabilization, it reportedly helps maintain ES cells in the undifferentiated state. We then performed DNA microarray analyses between the Tcl1-deficient and -expressing ES cells. The results revealed that Tcl1 expression downregulated a distinct group of genes, including Ndp52, whose expression is very high in blastocysts but reduced in the primitive ectoderm. Based on these results, we discuss the possible roles of Tcl1 in ES cells.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0071645</identifier><identifier>PMID: 23940776</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>AKT protein ; Analysis ; Animals ; Apoptosis ; Apoptosis - genetics ; Biology ; Blastocysts ; Cell cycle ; Cell Differentiation - genetics ; Cell Line ; Cell lines ; Cell Proliferation ; Cloning ; Deoxyribonucleic acid ; DNA ; DNA microarrays ; Ectoderm ; Embryo cells ; Embryonic stem cells ; Embryonic Stem Cells - cytology ; Embryonic Stem Cells - physiology ; Embryos ; Functional analysis ; Gene expression ; Gene Expression Profiling ; Gene Transfer Techniques ; Genes ; Genetic engineering ; Kinases ; Medicine ; Mice ; Mice, Knockout ; Microarray Analysis ; Phosphorylation ; Proto-Oncogene Proteins - physiology ; Rodents ; Signaling ; Stem cell transplantation ; Stem cells ; University graduates ; Wnt protein ; Wnt Signaling Pathway - genetics ; β-Catenin</subject><ispartof>PloS one, 2013-08, Vol.8 (8), p.e71645-e71645</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Miyazaki et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (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>2013 Miyazaki et al 2013 Miyazaki et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-de85c625e6c0b28eeab7050d414a783d0b3e1274c4b4696c9c21dde2a47210373</citedby><cites>FETCH-LOGICAL-c758t-de85c625e6c0b28eeab7050d414a783d0b3e1274c4b4696c9c21dde2a47210373</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/PMC3733782/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733782/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23868,27926,27927,53793,53795</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23940776$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Wutz, Anton</contributor><creatorcontrib>Miyazaki, Tatsushi</creatorcontrib><creatorcontrib>Miyazaki, Satsuki</creatorcontrib><creatorcontrib>Ashida, Masafumi</creatorcontrib><creatorcontrib>Tanaka, Tomofumi</creatorcontrib><creatorcontrib>Tashiro, Fumi</creatorcontrib><creatorcontrib>Miyazaki, Jun-ichi</creatorcontrib><title>Functional analysis of Tcl1 using Tcl1-deficient mouse embryonic stem cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Tcl1 is highly expressed in embryonic stem (ES) cells, but its expression rapidly decreases following differentiation. To assess Tcl1's roles in ES cells, we generated Tcl1-deficient and -overexpressing mouse ES cell lines. We found that Tcl1 was neither essential nor sufficient for maintaining the undifferentiated state. Tcl1 is reported to activate Akt and to enhance cell proliferation. We found that Tcl1 expression levels correlated positively with the proliferation rate and negatively with the apoptosis of ES cells, but did not affect Akt phosphorylation. On the other hand, the phosphorylation level of β-catenin decreased in response to Tcl1 overexpression. We measured the β-catenin activity using the TOPflash reporter assay, and found that wild-type ES cells had low activity, which Tcl1 overexpression enhanced 1.8-fold. When the canonical Wnt signaling is activated by β-catenin stabilization, it reportedly helps maintain ES cells in the undifferentiated state. We then performed DNA microarray analyses between the Tcl1-deficient and -expressing ES cells. The results revealed that Tcl1 expression downregulated a distinct group of genes, including Ndp52, whose expression is very high in blastocysts but reduced in the primitive ectoderm. Based on these results, we discuss the possible roles of Tcl1 in ES cells.</description><subject>AKT protein</subject><subject>Analysis</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - genetics</subject><subject>Biology</subject><subject>Blastocysts</subject><subject>Cell cycle</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Line</subject><subject>Cell lines</subject><subject>Cell Proliferation</subject><subject>Cloning</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA microarrays</subject><subject>Ectoderm</subject><subject>Embryo cells</subject><subject>Embryonic stem cells</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Embryonic Stem Cells - physiology</subject><subject>Embryos</subject><subject>Functional analysis</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Transfer Techniques</subject><subject>Genes</subject><subject>Genetic engineering</subject><subject>Kinases</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Microarray Analysis</subject><subject>Phosphorylation</subject><subject>Proto-Oncogene Proteins - physiology</subject><subject>Rodents</subject><subject>Signaling</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>University graduates</subject><subject>Wnt protein</subject><subject>Wnt Signaling Pathway - genetics</subject><subject>β-Catenin</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</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>eNqNkl-L1DAUxYso7rr6DUQLgujDjPnXpH0RlsXVwYUFXX0N6e3tTIa2GZNWnG9vutNdprIPEkhC8rsnyclJkpeULClX9MPWDb4zzXLnOlwSoqgU2aPklBacLSQj_PHR_CR5FsKWkIznUj5NThgvBFFKniZfL4cOeuuiUmpitw82pK5Ob6Ch6RBst76dLiqsLVjs-rR1Q8AU29LvXWchDT22KWDThOfJk9o0AV9M41ny4_LTzcWXxdX159XF-dUCVJb3USrPQLIMJZCS5YimVCQjlaDCqJxXpORImRIgSiELCQUwWlXIjFCMEq74WfL6oLtrXNCTD0FTwQkTihckEqsDUTmz1TtvW-P32hmrbxecX2vjewsN6gxJXqIyUGRcAHBTG1JJQUsiZQ5cRK2P02lD2WIF0QNvmpnofKezG712v3W8KVc5iwLvJgHvfg0Yet3aMBpmOoxexnszIqlQRRHRN_-gD79uotYmPsB2tYvnwiiqz4XKRfx2kUVq-QAVW4WthRia2sb1WcH7WUFkevzTr80Qgl59__b_7PXPOfv2iN2gafpNcM0wpi7MQXEAwbsQPNb3JlOix8zfuaHHzOsp87Hs1fEH3RfdhZz_BYDy-rQ</recordid><startdate>20130805</startdate><enddate>20130805</enddate><creator>Miyazaki, Tatsushi</creator><creator>Miyazaki, Satsuki</creator><creator>Ashida, Masafumi</creator><creator>Tanaka, Tomofumi</creator><creator>Tashiro, Fumi</creator><creator>Miyazaki, Jun-ichi</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>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>20130805</creationdate><title>Functional analysis of Tcl1 using Tcl1-deficient mouse embryonic stem cells</title><author>Miyazaki, Tatsushi ; Miyazaki, Satsuki ; Ashida, Masafumi ; Tanaka, Tomofumi ; Tashiro, Fumi ; Miyazaki, Jun-ichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-de85c625e6c0b28eeab7050d414a783d0b3e1274c4b4696c9c21dde2a47210373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>AKT protein</topic><topic>Analysis</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miyazaki, Tatsushi</au><au>Miyazaki, Satsuki</au><au>Ashida, Masafumi</au><au>Tanaka, Tomofumi</au><au>Tashiro, Fumi</au><au>Miyazaki, Jun-ichi</au><au>Wutz, Anton</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functional analysis of Tcl1 using Tcl1-deficient mouse embryonic stem cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-08-05</date><risdate>2013</risdate><volume>8</volume><issue>8</issue><spage>e71645</spage><epage>e71645</epage><pages>e71645-e71645</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Tcl1 is highly expressed in embryonic stem (ES) cells, but its expression rapidly decreases following differentiation. To assess Tcl1's roles in ES cells, we generated Tcl1-deficient and -overexpressing mouse ES cell lines. We found that Tcl1 was neither essential nor sufficient for maintaining the undifferentiated state. Tcl1 is reported to activate Akt and to enhance cell proliferation. We found that Tcl1 expression levels correlated positively with the proliferation rate and negatively with the apoptosis of ES cells, but did not affect Akt phosphorylation. On the other hand, the phosphorylation level of β-catenin decreased in response to Tcl1 overexpression. We measured the β-catenin activity using the TOPflash reporter assay, and found that wild-type ES cells had low activity, which Tcl1 overexpression enhanced 1.8-fold. When the canonical Wnt signaling is activated by β-catenin stabilization, it reportedly helps maintain ES cells in the undifferentiated state. We then performed DNA microarray analyses between the Tcl1-deficient and -expressing ES cells. The results revealed that Tcl1 expression downregulated a distinct group of genes, including Ndp52, whose expression is very high in blastocysts but reduced in the primitive ectoderm. Based on these results, we discuss the possible roles of Tcl1 in ES cells.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23940776</pmid><doi>10.1371/journal.pone.0071645</doi><tpages>e71645</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | AKT protein Analysis Animals Apoptosis Apoptosis - genetics Biology Blastocysts Cell cycle Cell Differentiation - genetics Cell Line Cell lines Cell Proliferation Cloning Deoxyribonucleic acid DNA DNA microarrays Ectoderm Embryo cells Embryonic stem cells Embryonic Stem Cells - cytology Embryonic Stem Cells - physiology Embryos Functional analysis Gene expression Gene Expression Profiling Gene Transfer Techniques Genes Genetic engineering Kinases Medicine Mice Mice, Knockout Microarray Analysis Phosphorylation Proto-Oncogene Proteins - physiology Rodents Signaling Stem cell transplantation Stem cells University graduates Wnt protein Wnt Signaling Pathway - genetics β-Catenin |
| title | Functional analysis of Tcl1 using Tcl1-deficient mouse embryonic stem cells |
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