Inhibition of Rho kinase regulates specification of early differentiation events in P19 embryonal carcinoma stem cells
The Rho kinase pathway plays a key role in many early cell/tissue determination events that take place in embryogenesis. Rho and its downstream effector Rho kinase (ROCK) play pivotal roles in cell migration, apoptosis (membrane blebbing), cell proliferation/cell cycle, cell-cell adhesion and gene r...
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| description | The Rho kinase pathway plays a key role in many early cell/tissue determination events that take place in embryogenesis. Rho and its downstream effector Rho kinase (ROCK) play pivotal roles in cell migration, apoptosis (membrane blebbing), cell proliferation/cell cycle, cell-cell adhesion and gene regulation. We and others have previously demonstrated that inhibition of ROCK blocks endoderm differentiation in embryonal carcinoma stem cells, however, the effect of ROCK inhibition on mesoderm and ectoderm specification has not been fully examined. In this study, the role of ROCK within the specification and differentiation of all three germ layers was examined.
P19 cells were treated with the specific ROCK inhibitor Y-27623, and increase in differentiation efficiency into neuro-ectodermal and mesodermal lineages was observed. However, as expected a dramatic decrease in early endodermal markers was observed when ROCK was inhibited. Interestingly, within these ROCK-inhibited RA treated cultures, increased levels of mesodermal or ectodermal markers were not observed, instead it was found that the pluripotent markers SSEA-1 and Oct-4 remained up-regulated similar to that seen in undifferentiated cultures. Using standard and widely accepted methods for reproducible P19 differentiation into all three germ layers, an enhancement of mesoderm and ectoderm differentiation with a concurrent loss of endoderm lineage specification was observed with Y-27632 treatment. Evidence would suggest that this effect is in part mediated through TGF-β and SMAD signaling as ROCK-inhibited cells displayed aberrant SMAD activation and did not return to a 'ground' state after the inhibition had been removed.
Given this data and the fact that only a partial rescue of normal differentiation capacity occurred when ROCK inhibition was alleviated, the effect of ROCK inhibition on the differentiation capacity of pluripotent cell populations should be further examined to elucidate the role of the Rho-ROCK pathway in early cellular 'fate' decision making processes. |
| doi_str_mv | 10.1371/journal.pone.0026484 |
| format | Article |
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P19 cells were treated with the specific ROCK inhibitor Y-27623, and increase in differentiation efficiency into neuro-ectodermal and mesodermal lineages was observed. However, as expected a dramatic decrease in early endodermal markers was observed when ROCK was inhibited. Interestingly, within these ROCK-inhibited RA treated cultures, increased levels of mesodermal or ectodermal markers were not observed, instead it was found that the pluripotent markers SSEA-1 and Oct-4 remained up-regulated similar to that seen in undifferentiated cultures. Using standard and widely accepted methods for reproducible P19 differentiation into all three germ layers, an enhancement of mesoderm and ectoderm differentiation with a concurrent loss of endoderm lineage specification was observed with Y-27632 treatment. Evidence would suggest that this effect is in part mediated through TGF-β and SMAD signaling as ROCK-inhibited cells displayed aberrant SMAD activation and did not return to a 'ground' state after the inhibition had been removed.
Given this data and the fact that only a partial rescue of normal differentiation capacity occurred when ROCK inhibition was alleviated, the effect of ROCK inhibition on the differentiation capacity of pluripotent cell populations should be further examined to elucidate the role of the Rho-ROCK pathway in early cellular 'fate' decision making processes.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0026484</identifier><identifier>PMID: 22140430</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aberration ; Amides - pharmacology ; Animals ; Apoptosis ; Binding sites ; Biochemistry ; Biology ; Biomarkers ; Bone morphogenetic proteins ; Breast cancer ; Carcinoma ; Cell adhesion ; Cell adhesion & migration ; Cell cycle ; Cell differentiation ; Cell Differentiation - drug effects ; Cell migration ; Cell proliferation ; Decision making ; Differentiation ; Ectoderm ; Embryogenesis ; Embryonal Carcinoma Stem Cells - enzymology ; Embryonal Carcinoma Stem Cells - pathology ; Embryonic growth stage ; Embryos ; Endoderm ; Endoderm - drug effects ; Endoderm - pathology ; Gene expression ; Gene regulation ; Genes ; Growth factors ; Humans ; Inhibition ; Kinases ; Mesoderm ; Mice ; Molecular biology ; Oct-4 protein ; Pluripotency ; Pluripotent Stem Cells - drug effects ; Pluripotent Stem Cells - pathology ; Protein Kinase Inhibitors - pharmacology ; Proteins ; Pyridines - pharmacology ; Rho-associated kinase ; rho-Associated Kinases - antagonists & inhibitors ; rho-Associated Kinases - metabolism ; Signal transduction ; Signal Transduction - drug effects ; Signaling ; Smad protein ; Specifications ; Stem cell research ; Stem cells ; Transforming growth factors ; Tretinoin - pharmacology</subject><ispartof>PloS one, 2011-11, Vol.6 (11), p.e26484-e26484</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Krawetz 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>Krawetz et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-de13c193aa8b14859e28b4579766fd616cb4a8ce15c6419d5e7fa86bf6a311fd3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227584/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227584/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27904,27905,53771,53773,79348,79349</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22140430$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Cooney, Austin John</contributor><creatorcontrib>Krawetz, Roman J</creatorcontrib><creatorcontrib>Taiani, Jaymi</creatorcontrib><creatorcontrib>Greene, Alexis</creatorcontrib><creatorcontrib>Kelly, Gregory M</creatorcontrib><creatorcontrib>Rancourt, Derrick E</creatorcontrib><title>Inhibition of Rho kinase regulates specification of early differentiation events in P19 embryonal carcinoma stem cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The Rho kinase pathway plays a key role in many early cell/tissue determination events that take place in embryogenesis. Rho and its downstream effector Rho kinase (ROCK) play pivotal roles in cell migration, apoptosis (membrane blebbing), cell proliferation/cell cycle, cell-cell adhesion and gene regulation. We and others have previously demonstrated that inhibition of ROCK blocks endoderm differentiation in embryonal carcinoma stem cells, however, the effect of ROCK inhibition on mesoderm and ectoderm specification has not been fully examined. In this study, the role of ROCK within the specification and differentiation of all three germ layers was examined.
P19 cells were treated with the specific ROCK inhibitor Y-27623, and increase in differentiation efficiency into neuro-ectodermal and mesodermal lineages was observed. However, as expected a dramatic decrease in early endodermal markers was observed when ROCK was inhibited. Interestingly, within these ROCK-inhibited RA treated cultures, increased levels of mesodermal or ectodermal markers were not observed, instead it was found that the pluripotent markers SSEA-1 and Oct-4 remained up-regulated similar to that seen in undifferentiated cultures. Using standard and widely accepted methods for reproducible P19 differentiation into all three germ layers, an enhancement of mesoderm and ectoderm differentiation with a concurrent loss of endoderm lineage specification was observed with Y-27632 treatment. Evidence would suggest that this effect is in part mediated through TGF-β and SMAD signaling as ROCK-inhibited cells displayed aberrant SMAD activation and did not return to a 'ground' state after the inhibition had been removed.
Given this data and the fact that only a partial rescue of normal differentiation capacity occurred when ROCK inhibition was alleviated, the effect of ROCK inhibition on the differentiation capacity of pluripotent cell populations should be further examined to elucidate the role of the Rho-ROCK pathway in early cellular 'fate' decision making processes.</description><subject>Aberration</subject><subject>Amides - pharmacology</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Binding sites</subject><subject>Biochemistry</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>Bone morphogenetic proteins</subject><subject>Breast cancer</subject><subject>Carcinoma</subject><subject>Cell adhesion</subject><subject>Cell adhesion & migration</subject><subject>Cell cycle</subject><subject>Cell differentiation</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell migration</subject><subject>Cell proliferation</subject><subject>Decision making</subject><subject>Differentiation</subject><subject>Ectoderm</subject><subject>Embryogenesis</subject><subject>Embryonal Carcinoma Stem Cells - enzymology</subject><subject>Embryonal Carcinoma Stem Cells - pathology</subject><subject>Embryonic growth stage</subject><subject>Embryos</subject><subject>Endoderm</subject><subject>Endoderm - drug effects</subject><subject>Endoderm - pathology</subject><subject>Gene expression</subject><subject>Gene regulation</subject><subject>Genes</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Inhibition</subject><subject>Kinases</subject><subject>Mesoderm</subject><subject>Mice</subject><subject>Molecular biology</subject><subject>Oct-4 protein</subject><subject>Pluripotency</subject><subject>Pluripotent Stem Cells - drug effects</subject><subject>Pluripotent Stem Cells - pathology</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Proteins</subject><subject>Pyridines - pharmacology</subject><subject>Rho-associated kinase</subject><subject>rho-Associated Kinases - antagonists & inhibitors</subject><subject>rho-Associated Kinases - metabolism</subject><subject>Signal transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Signaling</subject><subject>Smad protein</subject><subject>Specifications</subject><subject>Stem cell research</subject><subject>Stem cells</subject><subject>Transforming growth factors</subject><subject>Tretinoin - pharmacology</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</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>eNqNk12P1CAUhhujcdfVf2CUxETjxYxQKKU3JpuNH5Nssmb9uCUUDjOMbRmhnTj_XurMbKZmLwwXEHjOezgvnCx7TvCc0JK8W_shdKqZb3wHc4xzzgR7kJ2TiuYznmP68GR9lj2JcY1xQQXnj7OzPCcMM4rPs-2iW7na9c53yFt0u_Lop-tUBBRgOTSqh4jiBrSzTqsjBSo0O2SctRCg693-ALZpHZHr0BdSIWjrsPPpgkiroF3nW4ViDy3S0DTxafbIqibCs8N8kX3_-OHb1efZ9c2nxdXl9UzzivQzA4TqVIVSoiZMFBXkomZFWZWcW8MJ1zVTQgMpNGekMgWUVgleW64oIdbQi-zlXnfT-CgPlkVJKMGcJRmRiMWeMF6t5Sa4VoWd9MrJvxs-LKUKvdMNSFKzVLERJSOK4YIITkvDKm0Ix5WxOGm9P2Qb6haMTn4E1UxEpyedW8ml30qa52UhWBJ4cxAI_tcAsZeti6NhqgM_RFlhUdJU_Jjq1T_k_cUdqKVK93ed9SmtHjXlJSu54ISyMev8HioNA63T6XtZl_YnAW8nAYnp4Xe_VEOMcvH19v_Zmx9T9vUJuwLV9Kvom2H8XnEKsj2og48xgL3zmGA5dsfRDTl2hzx0Rwp7cfo-d0HHdqB_AOBwCy4</recordid><startdate>20111130</startdate><enddate>20111130</enddate><creator>Krawetz, Roman J</creator><creator>Taiani, Jaymi</creator><creator>Greene, Alexis</creator><creator>Kelly, Gregory M</creator><creator>Rancourt, Derrick E</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>20111130</creationdate><title>Inhibition of Rho kinase regulates specification of early differentiation events in P19 embryonal carcinoma stem cells</title><author>Krawetz, Roman J ; Taiani, Jaymi ; Greene, Alexis ; Kelly, Gregory M ; Rancourt, Derrick E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c691t-de13c193aa8b14859e28b4579766fd616cb4a8ce15c6419d5e7fa86bf6a311fd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Aberration</topic><topic>Amides - pharmacology</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Binding sites</topic><topic>Biochemistry</topic><topic>Biology</topic><topic>Biomarkers</topic><topic>Bone morphogenetic proteins</topic><topic>Breast cancer</topic><topic>Carcinoma</topic><topic>Cell adhesion</topic><topic>Cell adhesion & migration</topic><topic>Cell cycle</topic><topic>Cell differentiation</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell migration</topic><topic>Cell proliferation</topic><topic>Decision making</topic><topic>Differentiation</topic><topic>Ectoderm</topic><topic>Embryogenesis</topic><topic>Embryonal Carcinoma Stem Cells - enzymology</topic><topic>Embryonal Carcinoma Stem Cells - pathology</topic><topic>Embryonic growth stage</topic><topic>Embryos</topic><topic>Endoderm</topic><topic>Endoderm - drug effects</topic><topic>Endoderm - pathology</topic><topic>Gene expression</topic><topic>Gene regulation</topic><topic>Genes</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Inhibition</topic><topic>Kinases</topic><topic>Mesoderm</topic><topic>Mice</topic><topic>Molecular biology</topic><topic>Oct-4 protein</topic><topic>Pluripotency</topic><topic>Pluripotent Stem Cells - drug effects</topic><topic>Pluripotent Stem Cells - pathology</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Proteins</topic><topic>Pyridines - pharmacology</topic><topic>Rho-associated kinase</topic><topic>rho-Associated Kinases - antagonists & inhibitors</topic><topic>rho-Associated Kinases - metabolism</topic><topic>Signal transduction</topic><topic>Signal Transduction - drug effects</topic><topic>Signaling</topic><topic>Smad protein</topic><topic>Specifications</topic><topic>Stem cell research</topic><topic>Stem cells</topic><topic>Transforming growth factors</topic><topic>Tretinoin - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Krawetz, Roman J</creatorcontrib><creatorcontrib>Taiani, Jaymi</creatorcontrib><creatorcontrib>Greene, Alexis</creatorcontrib><creatorcontrib>Kelly, Gregory M</creatorcontrib><creatorcontrib>Rancourt, Derrick E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>TestCollectionTL3OpenAccess</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Krawetz, Roman J</au><au>Taiani, Jaymi</au><au>Greene, Alexis</au><au>Kelly, Gregory M</au><au>Rancourt, Derrick E</au><au>Cooney, Austin John</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of Rho kinase regulates specification of early differentiation events in P19 embryonal carcinoma stem cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-11-30</date><risdate>2011</risdate><volume>6</volume><issue>11</issue><spage>e26484</spage><epage>e26484</epage><pages>e26484-e26484</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The Rho kinase pathway plays a key role in many early cell/tissue determination events that take place in embryogenesis. Rho and its downstream effector Rho kinase (ROCK) play pivotal roles in cell migration, apoptosis (membrane blebbing), cell proliferation/cell cycle, cell-cell adhesion and gene regulation. We and others have previously demonstrated that inhibition of ROCK blocks endoderm differentiation in embryonal carcinoma stem cells, however, the effect of ROCK inhibition on mesoderm and ectoderm specification has not been fully examined. In this study, the role of ROCK within the specification and differentiation of all three germ layers was examined.
P19 cells were treated with the specific ROCK inhibitor Y-27623, and increase in differentiation efficiency into neuro-ectodermal and mesodermal lineages was observed. However, as expected a dramatic decrease in early endodermal markers was observed when ROCK was inhibited. Interestingly, within these ROCK-inhibited RA treated cultures, increased levels of mesodermal or ectodermal markers were not observed, instead it was found that the pluripotent markers SSEA-1 and Oct-4 remained up-regulated similar to that seen in undifferentiated cultures. Using standard and widely accepted methods for reproducible P19 differentiation into all three germ layers, an enhancement of mesoderm and ectoderm differentiation with a concurrent loss of endoderm lineage specification was observed with Y-27632 treatment. Evidence would suggest that this effect is in part mediated through TGF-β and SMAD signaling as ROCK-inhibited cells displayed aberrant SMAD activation and did not return to a 'ground' state after the inhibition had been removed.
Given this data and the fact that only a partial rescue of normal differentiation capacity occurred when ROCK inhibition was alleviated, the effect of ROCK inhibition on the differentiation capacity of pluripotent cell populations should be further examined to elucidate the role of the Rho-ROCK pathway in early cellular 'fate' decision making processes.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22140430</pmid><doi>10.1371/journal.pone.0026484</doi><tpages>e26484</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | PloS one, 2011-11, Vol.6 (11), p.e26484-e26484 |
| issn | 1932-6203 1932-6203 |
| language | eng |
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| source | MEDLINE; Public Library of Science (PLoS); TestCollectionTL3OpenAccess; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Aberration Amides - pharmacology Animals Apoptosis Binding sites Biochemistry Biology Biomarkers Bone morphogenetic proteins Breast cancer Carcinoma Cell adhesion Cell adhesion & migration Cell cycle Cell differentiation Cell Differentiation - drug effects Cell migration Cell proliferation Decision making Differentiation Ectoderm Embryogenesis Embryonal Carcinoma Stem Cells - enzymology Embryonal Carcinoma Stem Cells - pathology Embryonic growth stage Embryos Endoderm Endoderm - drug effects Endoderm - pathology Gene expression Gene regulation Genes Growth factors Humans Inhibition Kinases Mesoderm Mice Molecular biology Oct-4 protein Pluripotency Pluripotent Stem Cells - drug effects Pluripotent Stem Cells - pathology Protein Kinase Inhibitors - pharmacology Proteins Pyridines - pharmacology Rho-associated kinase rho-Associated Kinases - antagonists & inhibitors rho-Associated Kinases - metabolism Signal transduction Signal Transduction - drug effects Signaling Smad protein Specifications Stem cell research Stem cells Transforming growth factors Tretinoin - pharmacology |
| title | Inhibition of Rho kinase regulates specification of early differentiation events in P19 embryonal carcinoma stem cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-21T09%3A46%3A56IST&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=Inhibition%20of%20Rho%20kinase%20regulates%20specification%20of%20early%20differentiation%20events%20in%20P19%20embryonal%20carcinoma%20stem%20cells&rft.jtitle=PloS%20one&rft.au=Krawetz,%20Roman%20J&rft.date=2011-11-30&rft.volume=6&rft.issue=11&rft.spage=e26484&rft.epage=e26484&rft.pages=e26484-e26484&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0026484&rft_dat=%3Cgale_plos_%3EA476861344%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=1310647978&rft_id=info:pmid/22140430&rft_galeid=A476861344&rft_doaj_id=oai_doaj_org_article_1b4ffed8741a40518637d49cd1609df0&rfr_iscdi=true |