ILK induces cardiomyogenesis in the human heart
Integrin-linked kinase (ILK) is a widely conserved serine/threonine kinase that regulates diverse signal transduction pathways implicated in cardiac hypertrophy and contractility. In this study we explored whether experimental overexpression of ILK would up-regulate morphogenesis in the human fetal...
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description | Integrin-linked kinase (ILK) is a widely conserved serine/threonine kinase that regulates diverse signal transduction pathways implicated in cardiac hypertrophy and contractility. In this study we explored whether experimental overexpression of ILK would up-regulate morphogenesis in the human fetal heart.
Primary cultures of human fetal myocardial cells (19-22 weeks gestation) yielded scattered aggregates of cardioblasts positive for the early cardiac lineage marker nk × 2.5 and containing nascent sarcomeres. Cardiac cells in colonies uniformly expressed the gap junction protein connexin 43 (C × 43) and displayed a spectrum of differentiation with only a subset of cells exhibiting the late cardiomyogenic marker troponin T (cTnT) and evidence of electrical excitability. Adenovirus-mediated overexpression of ILK potently increased the number of new aggregates of primitive cardioblasts (p |
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Primary cultures of human fetal myocardial cells (19-22 weeks gestation) yielded scattered aggregates of cardioblasts positive for the early cardiac lineage marker nk × 2.5 and containing nascent sarcomeres. Cardiac cells in colonies uniformly expressed the gap junction protein connexin 43 (C × 43) and displayed a spectrum of differentiation with only a subset of cells exhibiting the late cardiomyogenic marker troponin T (cTnT) and evidence of electrical excitability. Adenovirus-mediated overexpression of ILK potently increased the number of new aggregates of primitive cardioblasts (p<0.001). The number of cardioblast colonies was significantly decreased (p<0.05) when ILK expression was knocked down with ILK targeted siRNA. Interestingly, overexpression of the activation resistant ILK mutant (ILK(R211A)) resulted in much greater increase in the number of new cell aggregates as compared to overexpression of wild-type ILK (ILK(WT)). The cardiomyogenic effects of ILK(R211A) and ILK(WT) were accompanied by concurrent activation of β-catenin (p<0.001) and increase expression of progenitor cell marker islet-1, which was also observed in lysates of transgenic mice with cardiac-specific over-expression of ILK(R211A) and ILK(WT). Finally, endogenous ILK expression was shown to increase in concert with those of cardiomyogenic markers during directed cardiomyogenic differentiation in human embryonic stem cells (hESCs).
In the human fetal heart ILK activation is instructive to the specification of mesodermal precursor cells towards a cardiomyogenic lineage. Induction of cardiomyogenesis by ILK overexpression bypasses the requirement of proximal PI3K activation for transduction of growth factor- and β1-integrin-mediated differentiation signals. Altogether, our data indicate that ILK represents a novel regulatory checkpoint during human cardiomyogenesis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0037802</identifier><identifier>PMID: 22666394</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>1-Phosphatidylinositol 3-kinase ; Activation ; Aggregates ; Biology ; Bone marrow ; Calcium-binding protein ; Cardiac Myosins ; Cardiology ; Cardiomyocytes ; Cell adhesion & migration ; Cell Aggregation ; Cell cycle ; Cellular signal transduction ; Colonies ; Connexin 43 ; Differentiation ; Electrophysiological Phenomena ; Embryo cells ; Embryonic stem cells ; Embryonic Stem Cells - cytology ; Embryonic Stem Cells - metabolism ; Enzyme Activation ; Excitability ; Female ; Fetus - cytology ; Fetuses ; Gene Expression Regulation ; Genetic engineering ; Genotype & phenotype ; Gestation ; Health care networks ; Heart ; Heart diseases ; Heart hypertrophy ; Humans ; Hypertrophy ; Hypoxia ; ILK protein ; Integrins ; Islet-1 protein ; Kinases ; LIM-Homeodomain Proteins - genetics ; Lysates ; Medical research ; Microscopy ; Morphogenesis ; Muscle contraction ; Myoblasts, Cardiac - cytology ; Myoblasts, Cardiac - metabolism ; Myocardium - cytology ; Myocardium - metabolism ; Myocytes, Cardiac - cytology ; Myocytes, Cardiac - metabolism ; Myosin Heavy Chains - metabolism ; Overexpression ; Phosphatidylinositol 3-Kinases - metabolism ; Physiology ; Pregnancy ; Progenitor cells ; Protein Transport ; Protein-Serine-Threonine Kinases - metabolism ; Protein-serine/threonine kinase ; Proteins ; Rodents ; Sarcomeres ; Sarcomeres - metabolism ; Signal transduction ; Stem cells ; Transcription Factors - genetics ; Transgenic mice ; Troponin ; Vascular endothelial growth factor</subject><ispartof>PloS one, 2012-05, Vol.7 (5), p.e37802-e37802</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Traister 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>Traister et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-6951c6a3f89f7afa820e650c7c335a0c2f6f1bcbc79543ab91acfa5e2c3ae07c3</citedby><cites>FETCH-LOGICAL-c692t-6951c6a3f89f7afa820e650c7c335a0c2f6f1bcbc79543ab91acfa5e2c3ae07c3</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/PMC3362604/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362604/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22666394$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Emanueli, Costanza</contributor><creatorcontrib>Traister, Alexandra</creatorcontrib><creatorcontrib>Aafaqi, Shabana</creatorcontrib><creatorcontrib>Masse, Stephane</creatorcontrib><creatorcontrib>Dai, Xiaojing</creatorcontrib><creatorcontrib>Li, Mark</creatorcontrib><creatorcontrib>Hinek, Aleksander</creatorcontrib><creatorcontrib>Nanthakumar, Kumaraswamy</creatorcontrib><creatorcontrib>Hannigan, Gregory</creatorcontrib><creatorcontrib>Coles, John G</creatorcontrib><title>ILK induces cardiomyogenesis in the human heart</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Integrin-linked kinase (ILK) is a widely conserved serine/threonine kinase that regulates diverse signal transduction pathways implicated in cardiac hypertrophy and contractility. In this study we explored whether experimental overexpression of ILK would up-regulate morphogenesis in the human fetal heart.
Primary cultures of human fetal myocardial cells (19-22 weeks gestation) yielded scattered aggregates of cardioblasts positive for the early cardiac lineage marker nk × 2.5 and containing nascent sarcomeres. Cardiac cells in colonies uniformly expressed the gap junction protein connexin 43 (C × 43) and displayed a spectrum of differentiation with only a subset of cells exhibiting the late cardiomyogenic marker troponin T (cTnT) and evidence of electrical excitability. Adenovirus-mediated overexpression of ILK potently increased the number of new aggregates of primitive cardioblasts (p<0.001). The number of cardioblast colonies was significantly decreased (p<0.05) when ILK expression was knocked down with ILK targeted siRNA. Interestingly, overexpression of the activation resistant ILK mutant (ILK(R211A)) resulted in much greater increase in the number of new cell aggregates as compared to overexpression of wild-type ILK (ILK(WT)). The cardiomyogenic effects of ILK(R211A) and ILK(WT) were accompanied by concurrent activation of β-catenin (p<0.001) and increase expression of progenitor cell marker islet-1, which was also observed in lysates of transgenic mice with cardiac-specific over-expression of ILK(R211A) and ILK(WT). Finally, endogenous ILK expression was shown to increase in concert with those of cardiomyogenic markers during directed cardiomyogenic differentiation in human embryonic stem cells (hESCs).
In the human fetal heart ILK activation is instructive to the specification of mesodermal precursor cells towards a cardiomyogenic lineage. Induction of cardiomyogenesis by ILK overexpression bypasses the requirement of proximal PI3K activation for transduction of growth factor- and β1-integrin-mediated differentiation signals. Altogether, our data indicate that ILK represents a novel regulatory checkpoint during human cardiomyogenesis.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>Activation</subject><subject>Aggregates</subject><subject>Biology</subject><subject>Bone marrow</subject><subject>Calcium-binding protein</subject><subject>Cardiac Myosins</subject><subject>Cardiology</subject><subject>Cardiomyocytes</subject><subject>Cell adhesion & migration</subject><subject>Cell Aggregation</subject><subject>Cell cycle</subject><subject>Cellular signal transduction</subject><subject>Colonies</subject><subject>Connexin 43</subject><subject>Differentiation</subject><subject>Electrophysiological Phenomena</subject><subject>Embryo cells</subject><subject>Embryonic stem cells</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>Enzyme Activation</subject><subject>Excitability</subject><subject>Female</subject><subject>Fetus - cytology</subject><subject>Fetuses</subject><subject>Gene Expression Regulation</subject><subject>Genetic engineering</subject><subject>Genotype & phenotype</subject><subject>Gestation</subject><subject>Health care networks</subject><subject>Heart</subject><subject>Heart diseases</subject><subject>Heart hypertrophy</subject><subject>Humans</subject><subject>Hypertrophy</subject><subject>Hypoxia</subject><subject>ILK protein</subject><subject>Integrins</subject><subject>Islet-1 protein</subject><subject>Kinases</subject><subject>LIM-Homeodomain Proteins - genetics</subject><subject>Lysates</subject><subject>Medical research</subject><subject>Microscopy</subject><subject>Morphogenesis</subject><subject>Muscle contraction</subject><subject>Myoblasts, Cardiac - cytology</subject><subject>Myoblasts, Cardiac - metabolism</subject><subject>Myocardium - cytology</subject><subject>Myocardium - metabolism</subject><subject>Myocytes, Cardiac - cytology</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Myosin Heavy Chains - metabolism</subject><subject>Overexpression</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Physiology</subject><subject>Pregnancy</subject><subject>Progenitor cells</subject><subject>Protein Transport</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Protein-serine/threonine kinase</subject><subject>Proteins</subject><subject>Rodents</subject><subject>Sarcomeres</subject><subject>Sarcomeres - metabolism</subject><subject>Signal transduction</subject><subject>Stem cells</subject><subject>Transcription Factors - genetics</subject><subject>Transgenic mice</subject><subject>Troponin</subject><subject>Vascular endothelial growth factor</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</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>eNqNkluL1DAUx4so7kW_gWhBEH2Y2VyapH0RlsXL4MCCt9dwmiZthrYZk1bcb7-p012msg-Sh4ST3_mfc5J_krzAaI2pwBc7N_oe2vXe9XqNEBU5Io-SU1xQsuIE0cdH55PkLIQdQozmnD9NTgjhnNMiO00uNtsvqe2rUemQKvCVdd2Nq3Wvgw3xIh0anTZjB33aaPDDs-SJgTbo5_N-nvz4-OH71efV9vrT5upyu1K8IMOKFwwrDtTkhRFgICdIc4aUUJQyQIoYbnCpSiUKllEoCwzKANNEUdAoUufJq4PuvnVBzrMGiSlhiOA855HYHIjKwU7uve3A30gHVv4NOF_L2K9VrZZYlGBMTiskWJaJPBdxdlpWwMBUpISo9X6uNpadrpTuBw_tQnR509tG1u63pJQTjrIo8HYW8O7XqMMgOxuUblvotRtj32jqGVHOIvr6H_Th6WaqhjiA7Y2LddUkKi8zIRDKMJ_Krh-g4qp0Z1U0hrExvkh4t0iIzKD_DDWMIcjNt6__z17_XLJvjtjolHZogmvHwbo-LMHsACrvQvDa3D8yRnLy9d1ryMnXcvZ1THt5_EH3SXdGpreLsvE3</recordid><startdate>20120529</startdate><enddate>20120529</enddate><creator>Traister, Alexandra</creator><creator>Aafaqi, Shabana</creator><creator>Masse, Stephane</creator><creator>Dai, Xiaojing</creator><creator>Li, Mark</creator><creator>Hinek, Aleksander</creator><creator>Nanthakumar, Kumaraswamy</creator><creator>Hannigan, Gregory</creator><creator>Coles, John G</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>20120529</creationdate><title>ILK induces cardiomyogenesis in the human heart</title><author>Traister, Alexandra ; Aafaqi, Shabana ; Masse, Stephane ; Dai, Xiaojing ; Li, Mark ; Hinek, Aleksander ; Nanthakumar, Kumaraswamy ; Hannigan, Gregory ; Coles, John G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-6951c6a3f89f7afa820e650c7c335a0c2f6f1bcbc79543ab91acfa5e2c3ae07c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>Activation</topic><topic>Aggregates</topic><topic>Biology</topic><topic>Bone marrow</topic><topic>Calcium-binding protein</topic><topic>Cardiac Myosins</topic><topic>Cardiology</topic><topic>Cardiomyocytes</topic><topic>Cell adhesion & migration</topic><topic>Cell Aggregation</topic><topic>Cell cycle</topic><topic>Cellular signal transduction</topic><topic>Colonies</topic><topic>Connexin 43</topic><topic>Differentiation</topic><topic>Electrophysiological Phenomena</topic><topic>Embryo cells</topic><topic>Embryonic stem cells</topic><topic>Embryonic Stem Cells - cytology</topic><topic>Embryonic Stem Cells - metabolism</topic><topic>Enzyme Activation</topic><topic>Excitability</topic><topic>Female</topic><topic>Fetus - cytology</topic><topic>Fetuses</topic><topic>Gene Expression Regulation</topic><topic>Genetic engineering</topic><topic>Genotype & phenotype</topic><topic>Gestation</topic><topic>Health care networks</topic><topic>Heart</topic><topic>Heart diseases</topic><topic>Heart hypertrophy</topic><topic>Humans</topic><topic>Hypertrophy</topic><topic>Hypoxia</topic><topic>ILK protein</topic><topic>Integrins</topic><topic>Islet-1 protein</topic><topic>Kinases</topic><topic>LIM-Homeodomain Proteins - genetics</topic><topic>Lysates</topic><topic>Medical research</topic><topic>Microscopy</topic><topic>Morphogenesis</topic><topic>Muscle contraction</topic><topic>Myoblasts, Cardiac - cytology</topic><topic>Myoblasts, Cardiac - metabolism</topic><topic>Myocardium - cytology</topic><topic>Myocardium - metabolism</topic><topic>Myocytes, Cardiac - cytology</topic><topic>Myocytes, Cardiac - 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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>Traister, Alexandra</au><au>Aafaqi, Shabana</au><au>Masse, Stephane</au><au>Dai, Xiaojing</au><au>Li, Mark</au><au>Hinek, Aleksander</au><au>Nanthakumar, Kumaraswamy</au><au>Hannigan, Gregory</au><au>Coles, John G</au><au>Emanueli, Costanza</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ILK induces cardiomyogenesis in the human heart</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-05-29</date><risdate>2012</risdate><volume>7</volume><issue>5</issue><spage>e37802</spage><epage>e37802</epage><pages>e37802-e37802</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Integrin-linked kinase (ILK) is a widely conserved serine/threonine kinase that regulates diverse signal transduction pathways implicated in cardiac hypertrophy and contractility. In this study we explored whether experimental overexpression of ILK would up-regulate morphogenesis in the human fetal heart.
Primary cultures of human fetal myocardial cells (19-22 weeks gestation) yielded scattered aggregates of cardioblasts positive for the early cardiac lineage marker nk × 2.5 and containing nascent sarcomeres. Cardiac cells in colonies uniformly expressed the gap junction protein connexin 43 (C × 43) and displayed a spectrum of differentiation with only a subset of cells exhibiting the late cardiomyogenic marker troponin T (cTnT) and evidence of electrical excitability. Adenovirus-mediated overexpression of ILK potently increased the number of new aggregates of primitive cardioblasts (p<0.001). The number of cardioblast colonies was significantly decreased (p<0.05) when ILK expression was knocked down with ILK targeted siRNA. Interestingly, overexpression of the activation resistant ILK mutant (ILK(R211A)) resulted in much greater increase in the number of new cell aggregates as compared to overexpression of wild-type ILK (ILK(WT)). The cardiomyogenic effects of ILK(R211A) and ILK(WT) were accompanied by concurrent activation of β-catenin (p<0.001) and increase expression of progenitor cell marker islet-1, which was also observed in lysates of transgenic mice with cardiac-specific over-expression of ILK(R211A) and ILK(WT). Finally, endogenous ILK expression was shown to increase in concert with those of cardiomyogenic markers during directed cardiomyogenic differentiation in human embryonic stem cells (hESCs).
In the human fetal heart ILK activation is instructive to the specification of mesodermal precursor cells towards a cardiomyogenic lineage. Induction of cardiomyogenesis by ILK overexpression bypasses the requirement of proximal PI3K activation for transduction of growth factor- and β1-integrin-mediated differentiation signals. Altogether, our data indicate that ILK represents a novel regulatory checkpoint during human cardiomyogenesis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22666394</pmid><doi>10.1371/journal.pone.0037802</doi><tpages>e37802</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2012-05, Vol.7 (5), p.e37802-e37802 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_1325021886 |
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 | 1-Phosphatidylinositol 3-kinase Activation Aggregates Biology Bone marrow Calcium-binding protein Cardiac Myosins Cardiology Cardiomyocytes Cell adhesion & migration Cell Aggregation Cell cycle Cellular signal transduction Colonies Connexin 43 Differentiation Electrophysiological Phenomena Embryo cells Embryonic stem cells Embryonic Stem Cells - cytology Embryonic Stem Cells - metabolism Enzyme Activation Excitability Female Fetus - cytology Fetuses Gene Expression Regulation Genetic engineering Genotype & phenotype Gestation Health care networks Heart Heart diseases Heart hypertrophy Humans Hypertrophy Hypoxia ILK protein Integrins Islet-1 protein Kinases LIM-Homeodomain Proteins - genetics Lysates Medical research Microscopy Morphogenesis Muscle contraction Myoblasts, Cardiac - cytology Myoblasts, Cardiac - metabolism Myocardium - cytology Myocardium - metabolism Myocytes, Cardiac - cytology Myocytes, Cardiac - metabolism Myosin Heavy Chains - metabolism Overexpression Phosphatidylinositol 3-Kinases - metabolism Physiology Pregnancy Progenitor cells Protein Transport Protein-Serine-Threonine Kinases - metabolism Protein-serine/threonine kinase Proteins Rodents Sarcomeres Sarcomeres - metabolism Signal transduction Stem cells Transcription Factors - genetics Transgenic mice Troponin Vascular endothelial growth factor |
title | ILK induces cardiomyogenesis in the human heart |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-21T13%3A52%3A36IST&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=ILK%20induces%20cardiomyogenesis%20in%20the%20human%20heart&rft.jtitle=PloS%20one&rft.au=Traister,%20Alexandra&rft.date=2012-05-29&rft.volume=7&rft.issue=5&rft.spage=e37802&rft.epage=e37802&rft.pages=e37802-e37802&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0037802&rft_dat=%3Cgale_plos_%3EA477004164%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=1325021886&rft_id=info:pmid/22666394&rft_galeid=A477004164&rft_doaj_id=oai_doaj_org_article_17baff83d0754478873943bda5afd2ba&rfr_iscdi=true |