β-catenin functions pleiotropically in differentiation and tumorigenesis in mouse embryo-derived stem cells
The canonical Wnt/β-catenin signaling pathway plays a crucial role in the maintenance of the balance between proliferation and differentiation throughout embryogenesis and tissue homeostasis. β-Catenin, encoded by the Ctnnb1 gene, mediates an intracellular signaling cascade activated by Wnt. It also...
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| creator | Okumura, Noriko Akutsu, Hidenori Sugawara, Tohru Miura, Takumi Takezawa, Youki Hosoda, Akihiro Yoshida, Keiichi Ichida, Justin K Yamada, Mitsutoshi Hamatani, Toshio Kuji, Naoaki Miyado, Kenji Yoshimura, Yasunori Umezawa, Akihiro |
| description | The canonical Wnt/β-catenin signaling pathway plays a crucial role in the maintenance of the balance between proliferation and differentiation throughout embryogenesis and tissue homeostasis. β-Catenin, encoded by the Ctnnb1 gene, mediates an intracellular signaling cascade activated by Wnt. It also plays an important role in the maintenance of various types of stem cells including adult stem cells and cancer stem cells. However, it is unclear if β-catenin is required for the derivation of mouse embryo-derived stem cells. Here, we established β-catenin-deficient (β-cat(Δ/Δ)) mouse embryo-derived stem cells and showed that β-catenin is not essential for acquiring self-renewal potential in the derivation of mouse embryonic stem cells (ESCs). However, teratomas formed from embryo-derived β-cat(Δ/Δ) ESCs were immature germ cell tumors without multilineage differentiated cell types. Re-expression of functional β-catenin eliminated their neoplastic, transformed phenotype and restored pluripotency, thereby rescuing the mutant ESCs. Our findings demonstrate that β-catenin has pleiotropic effects in ESCs; it is required for the differentiation of ESCs and prevents them from acquiring tumorigenic character. These results highlight β-catenin as the gatekeeper in differentiation and tumorigenesis in ESCs. |
| doi_str_mv | 10.1371/journal.pone.0063265 |
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It also plays an important role in the maintenance of various types of stem cells including adult stem cells and cancer stem cells. However, it is unclear if β-catenin is required for the derivation of mouse embryo-derived stem cells. Here, we established β-catenin-deficient (β-cat(Δ/Δ)) mouse embryo-derived stem cells and showed that β-catenin is not essential for acquiring self-renewal potential in the derivation of mouse embryonic stem cells (ESCs). However, teratomas formed from embryo-derived β-cat(Δ/Δ) ESCs were immature germ cell tumors without multilineage differentiated cell types. Re-expression of functional β-catenin eliminated their neoplastic, transformed phenotype and restored pluripotency, thereby rescuing the mutant ESCs. Our findings demonstrate that β-catenin has pleiotropic effects in ESCs; it is required for the differentiation of ESCs and prevents them from acquiring tumorigenic character. These results highlight β-catenin as the gatekeeper in differentiation and tumorigenesis in ESCs.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0063265</identifier><identifier>PMID: 23691006</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; beta Catenin - deficiency ; beta Catenin - genetics ; beta Catenin - metabolism ; Biology ; Blastocyst - cytology ; Blastocyst - pathology ; Cancer ; Carcinogenesis - genetics ; Cell Differentiation - genetics ; Cell self-renewal ; CTNNB1 gene ; Derivation ; Differentiation ; Embryo cells ; Embryogenesis ; Embryonic growth stage ; Embryonic Stem Cells - cytology ; Embryonic Stem Cells - metabolism ; Embryonic Stem Cells - pathology ; Embryos ; Exons - genetics ; Female ; Gene Deletion ; Genetic Pleiotropy ; Homeostasis ; Intracellular signalling ; Kinases ; Male ; Medicine ; Mice ; Mice, Inbred C57BL ; Mutation ; Pluripotency ; Signal transduction ; Stem cell transplantation ; Stem cells ; Teratoma - genetics ; Teratoma - pathology ; Tumorigenesis ; Tumors ; Wnt protein ; β-Catenin</subject><ispartof>PloS one, 2013-05, Vol.8 (5), p.e63265</ispartof><rights>2013 Okumura 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. 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genetics</subject><subject>Teratoma - pathology</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><subject>Wnt protein</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>eNp1Us2K1TAULqI449U3EC247jXJSdN2I8jgz8CAG12HNDm55pImNWkH7mv5ID6TrbczzCxcJeR8fzl8RfGakj2Fhr4_xjkF5fdjDLgnRAAT9ZPiknbAKsEIPH1wvyhe5HwkpIZWiOfFBQPR0YVzWfg_vyutJgwulHYOenIx5HL06OKU4ui08v5ULkPjrMWEYXJqxZQqmHKah5jcAQNml1fQEOeMJQ59OsXKYHK3aMo84VBq9D6_LJ5Z5TO-2s5d8ePzp-9XX6ubb1-urz7eVLpmYqo6IVitsOa2MT00QtuuptASAE21FhSgQ95rSo1tBTXcIue6Uwzq5b-WIOyKt2fd0ccst0VlSWGR4YLWbEFcnxEmqqMckxtUOsmonPz3ENNBqjQ57VESDqwTxvKW2cWnb9um0T0QbLDr11C74sPmNvcDGr3sKCn_SPTxJLif8hBvJYgaOr6GebcJpPhrxjz9JzI_o3SKOSe09w6UyLURdyy5NkJujVhobx6muyfdVQD-Aow_t10</recordid><startdate>20130514</startdate><enddate>20130514</enddate><creator>Okumura, Noriko</creator><creator>Akutsu, Hidenori</creator><creator>Sugawara, Tohru</creator><creator>Miura, Takumi</creator><creator>Takezawa, Youki</creator><creator>Hosoda, Akihiro</creator><creator>Yoshida, Keiichi</creator><creator>Ichida, Justin K</creator><creator>Yamada, Mitsutoshi</creator><creator>Hamatani, Toshio</creator><creator>Kuji, Naoaki</creator><creator>Miyado, Kenji</creator><creator>Yoshimura, Yasunori</creator><creator>Umezawa, Akihiro</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>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>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130514</creationdate><title>β-catenin functions pleiotropically in differentiation and tumorigenesis in mouse embryo-derived stem cells</title><author>Okumura, Noriko ; Akutsu, Hidenori ; Sugawara, Tohru ; Miura, Takumi ; Takezawa, Youki ; Hosoda, Akihiro ; Yoshida, Keiichi ; Ichida, Justin K ; Yamada, Mitsutoshi ; Hamatani, Toshio ; Kuji, Naoaki ; Miyado, Kenji ; Yoshimura, Yasunori ; Umezawa, Akihiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-96625ae54f7db376cf95138033c1cc61339e4bc11df861d4fe44c9a235932f0e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>beta Catenin - 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It also plays an important role in the maintenance of various types of stem cells including adult stem cells and cancer stem cells. However, it is unclear if β-catenin is required for the derivation of mouse embryo-derived stem cells. Here, we established β-catenin-deficient (β-cat(Δ/Δ)) mouse embryo-derived stem cells and showed that β-catenin is not essential for acquiring self-renewal potential in the derivation of mouse embryonic stem cells (ESCs). However, teratomas formed from embryo-derived β-cat(Δ/Δ) ESCs were immature germ cell tumors without multilineage differentiated cell types. Re-expression of functional β-catenin eliminated their neoplastic, transformed phenotype and restored pluripotency, thereby rescuing the mutant ESCs. Our findings demonstrate that β-catenin has pleiotropic effects in ESCs; it is required for the differentiation of ESCs and prevents them from acquiring tumorigenic character. These results highlight β-catenin as the gatekeeper in differentiation and tumorigenesis in ESCs.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23691006</pmid><doi>10.1371/journal.pone.0063265</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-05, Vol.8 (5), p.e63265 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1351346152 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animals beta Catenin - deficiency beta Catenin - genetics beta Catenin - metabolism Biology Blastocyst - cytology Blastocyst - pathology Cancer Carcinogenesis - genetics Cell Differentiation - genetics Cell self-renewal CTNNB1 gene Derivation Differentiation Embryo cells Embryogenesis Embryonic growth stage Embryonic Stem Cells - cytology Embryonic Stem Cells - metabolism Embryonic Stem Cells - pathology Embryos Exons - genetics Female Gene Deletion Genetic Pleiotropy Homeostasis Intracellular signalling Kinases Male Medicine Mice Mice, Inbred C57BL Mutation Pluripotency Signal transduction Stem cell transplantation Stem cells Teratoma - genetics Teratoma - pathology Tumorigenesis Tumors Wnt protein β-Catenin |
| title | β-catenin functions pleiotropically in differentiation and tumorigenesis in mouse embryo-derived stem cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T17%3A41%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=%CE%B2-catenin%20functions%20pleiotropically%20in%20differentiation%20and%20tumorigenesis%20in%20mouse%20embryo-derived%20stem%20cells&rft.jtitle=PloS%20one&rft.au=Okumura,%20Noriko&rft.date=2013-05-14&rft.volume=8&rft.issue=5&rft.spage=e63265&rft.pages=e63265-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0063265&rft_dat=%3Cproquest_plos_%3E2970840991%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1351346152&rft_id=info:pmid/23691006&rft_doaj_id=oai_doaj_org_article_043296df482f44cb8877cb30e7e9b803&rfr_iscdi=true |