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Article: Study of transforming growth factor alpha for the maintenance of human embryonic stem cells

TitleStudy of transforming growth factor alpha for the maintenance of human embryonic stem cells
Authors
KeywordsFeeder Cell
Growth Factor
Human Embryonic Stem Cell
Transforming Growth Factor Α
Issue Date2012
PublisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00441/index.htm
Citation
Cell And Tissue Research, 2012, v. 350 n. 2, p. 289-303 How to Cite?
AbstractHuman embryonic stem cells (hESCs) have great potential for regenerative medicine as they have selfregenerative and pluripotent properties. Feeder cells or their conditioned medium are required for the maintenance of hESC in the undifferentiated state. Feeder cells have been postulated to produce growth factors and extracellular molecules for maintaining hESC in culture. The present study has aimed at identifying these molecules. The gene expression of supportive feeder cells, namely human foreskin fibroblast (hFF-1) and non-supportive human lung fibroblast (WI-38) was analyzed by microarray and 445 genes were found to be differentially expressed. Gene ontology analysis showed that 20.9% and 15.5% of the products of these genes belonged to the extracellular region and regulation of transcription activity, respectively. After validation of selected differentially expressed genes in both human and mouse feeder cells, transforming growth factor a (TGFa) was chosen for functional study. The results demonstrated that knockdown or protein neutralization of TGFa in hFF-1 led to increased expression of early differentiation markers and lower attachment rates of hESC. More importantly, TGFa maintained pluripotent gene expression levels, attachment rates and pluripotency by the in vitro differentiation of H9 under non-supportive conditions. TGFa treatment activated the p44/42MAPK pathway but not the PI3K/Akt pathway. In addition, TGFa treatment increased the expression of pluripotent markers, NANOG and SSEA-3 but had no effects on the proliferation of hESCs. This study of the functional role of TGFa provides insights for the development of clinical grade hESCs for therapeutic applications. © The Author(s) 2012. © Springer-Verlag 2012.
Persistent Identifierhttp://hdl.handle.net/10722/173379
ISSN
2015 Impact Factor: 2.948
2015 SCImago Journal Rankings: 1.539
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChen, ACHen_HK
dc.contributor.authorLee, YLen_HK
dc.contributor.authorHou, DYCen_HK
dc.contributor.authorFong, SWen_HK
dc.contributor.authorPeng, Qen_HK
dc.contributor.authorPang, RTKen_HK
dc.contributor.authorChiu, PCNen_HK
dc.contributor.authorHo, PCen_HK
dc.contributor.authorLee, KFen_HK
dc.contributor.authorYeung, WSBen_HK
dc.date.accessioned2012-10-30T06:29:57Z-
dc.date.available2012-10-30T06:29:57Z-
dc.date.issued2012en_HK
dc.identifier.citationCell And Tissue Research, 2012, v. 350 n. 2, p. 289-303en_HK
dc.identifier.issn0302-766Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/173379-
dc.description.abstractHuman embryonic stem cells (hESCs) have great potential for regenerative medicine as they have selfregenerative and pluripotent properties. Feeder cells or their conditioned medium are required for the maintenance of hESC in the undifferentiated state. Feeder cells have been postulated to produce growth factors and extracellular molecules for maintaining hESC in culture. The present study has aimed at identifying these molecules. The gene expression of supportive feeder cells, namely human foreskin fibroblast (hFF-1) and non-supportive human lung fibroblast (WI-38) was analyzed by microarray and 445 genes were found to be differentially expressed. Gene ontology analysis showed that 20.9% and 15.5% of the products of these genes belonged to the extracellular region and regulation of transcription activity, respectively. After validation of selected differentially expressed genes in both human and mouse feeder cells, transforming growth factor a (TGFa) was chosen for functional study. The results demonstrated that knockdown or protein neutralization of TGFa in hFF-1 led to increased expression of early differentiation markers and lower attachment rates of hESC. More importantly, TGFa maintained pluripotent gene expression levels, attachment rates and pluripotency by the in vitro differentiation of H9 under non-supportive conditions. TGFa treatment activated the p44/42MAPK pathway but not the PI3K/Akt pathway. In addition, TGFa treatment increased the expression of pluripotent markers, NANOG and SSEA-3 but had no effects on the proliferation of hESCs. This study of the functional role of TGFa provides insights for the development of clinical grade hESCs for therapeutic applications. © The Author(s) 2012. © Springer-Verlag 2012.en_HK
dc.languageengen_US
dc.publisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00441/index.htmen_HK
dc.relation.ispartofCell and Tissue Researchen_HK
dc.rightsThe original publication is available at www.springerlink.com-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectFeeder Cellen_US
dc.subjectGrowth Factoren_US
dc.subjectHuman Embryonic Stem Cellen_US
dc.subjectTransforming Growth Factor Αen_US
dc.subject.meshAnimalsen_HK
dc.subject.meshCell Differentiation - physiologyen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshEmbryonic Stem Cells - cytology - metabolism - physiologyen_HK
dc.subject.meshFibroblasts - cytology - metabolism - physiologyen_HK
dc.subject.meshForeskin - cytologyen_HK
dc.subject.meshGene Expression Profilingen_HK
dc.subject.meshGene Knockdown Techniquesen_HK
dc.subject.meshHumansen_HK
dc.subject.meshLung - cytologyen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiceen_HK
dc.subject.meshNIH 3T3 Cellsen_HK
dc.subject.meshTransfectionen_HK
dc.subject.meshTransforming Growth Factor alpha - deficiency - metabolismen_HK
dc.titleStudy of transforming growth factor alpha for the maintenance of human embryonic stem cellsen_HK
dc.typeArticleen_HK
dc.identifier.emailLee, YL: cherielee@hku.hken_HK
dc.identifier.emailPang, RTK: rtkpang@hku.hken_HK
dc.identifier.emailChiu, PCN: pchiucn@hku.hken_HK
dc.identifier.emailLee, KF: ckflee@hku.hken_HK
dc.identifier.authorityLee, YL=rp00308en_HK
dc.identifier.authorityPang, RTK=rp01761en_HK
dc.identifier.authorityChiu, PCN=rp00424en_HK
dc.identifier.authorityLee, KF=rp00458en_HK
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1007/s00441-012-1476-7en_HK
dc.identifier.pmid22864984en_HK
dc.identifier.scopuseid_2-s2.0-84871183884en_HK
dc.identifier.hkuros222500-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84871183884&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume350en_HK
dc.identifier.issue2en_HK
dc.identifier.spage289en_HK
dc.identifier.epage303en_HK
dc.identifier.isiWOS:000310224300009-
dc.publisher.placeGermanyen_HK
dc.identifier.scopusauthoridChen, ACH=55325409600en_HK
dc.identifier.scopusauthoridLee, YL=15033851800en_HK
dc.identifier.scopusauthoridHou, DYC=55325868000en_HK
dc.identifier.scopusauthoridFong, SW=7102256321en_HK
dc.identifier.scopusauthoridPeng, Q=55324657100en_HK
dc.identifier.scopusauthoridPang, RTK=7004376636en_HK
dc.identifier.scopusauthoridChiu, PCN=25959969200en_HK
dc.identifier.scopusauthoridHo, PC=55628575265en_HK
dc.identifier.scopusauthoridLee, KF=26643097500en_HK
dc.identifier.scopusauthoridYeung, WSB=55763794781en_HK
dc.identifier.citeulike11029891-

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