A FOXM1 Dependent Mesenchymal-Epithelial Transition in Retinal Pigment Epithelium Cells
The integrity of the epithelium is maintained by a complex but regulated interplay of processes that allow conversion of a proliferative state into a stably differentiated state. In this study, using human embryonic stem cell (hESC) derived Retinal Pigment Epithelium (RPE) cells as a model; we have...
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| Veröffentlicht in: | PloS one 2015-06, Vol.10 (6), p.e0130379-e0130379 |
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| creator | Choudhary, Parul Dodsworth, Benjamin Thomas Sidders, Ben Gutteridge, Alex Michaelides, Christos Duckworth, Joshua Kane Whiting, Paul John Benn, Caroline Louise |
| description | The integrity of the epithelium is maintained by a complex but regulated interplay of processes that allow conversion of a proliferative state into a stably differentiated state. In this study, using human embryonic stem cell (hESC) derived Retinal Pigment Epithelium (RPE) cells as a model; we have investigated the molecular mechanisms that affect attainment of the epithelial phenotype. We demonstrate that RPE undergo a Mesenchymal-Epithelial Transition in culture before acquiring an epithelial phenotype in a FOXM1 dependent manner. We show that FOXM1 directly regulates proliferation of RPE through transcriptional control of cell cycle associated genes. Additionally, FOXM1 modulates expression of the signaling ligands BMP7 and Wnt5B which act reciprocally to enable epithelialization. This data uncovers a novel effect of FOXM1 dependent activities in contributing towards epithelial fate acquisition and furthers our understanding of the molecular regulators of a cell type that is currently being evaluated as a cell therapy. |
| doi_str_mv | 10.1371/journal.pone.0130379 |
| format | Article |
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In this study, using human embryonic stem cell (hESC) derived Retinal Pigment Epithelium (RPE) cells as a model; we have investigated the molecular mechanisms that affect attainment of the epithelial phenotype. We demonstrate that RPE undergo a Mesenchymal-Epithelial Transition in culture before acquiring an epithelial phenotype in a FOXM1 dependent manner. We show that FOXM1 directly regulates proliferation of RPE through transcriptional control of cell cycle associated genes. Additionally, FOXM1 modulates expression of the signaling ligands BMP7 and Wnt5B which act reciprocally to enable epithelialization. This data uncovers a novel effect of FOXM1 dependent activities in contributing towards epithelial fate acquisition and furthers our understanding of the molecular regulators of a cell type that is currently being evaluated as a cell therapy.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0130379</identifier><identifier>PMID: 26121260</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Bone Morphogenetic Protein 7 - metabolism ; Cancer ; Cell culture ; Cell cycle ; Cell Differentiation - drug effects ; Cell Lineage ; Cell Proliferation ; Embryonic Stem Cells - cytology ; Epithelial Cells - pathology ; Epithelial-Mesenchymal Transition ; Epithelium ; Forkhead Box Protein M1 ; Forkhead Transcription Factors - metabolism ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation ; Homeostasis ; Humans ; Kinases ; Life assessment ; Ligands ; Macular degeneration ; Mesenchyme ; Metastasis ; Molecular chains ; Molecular modelling ; Neurons - metabolism ; Phase transitions ; Phenotype ; Phenotypes ; Proteins ; Regulators ; Retina ; Retinal pigment epithelium ; Retinal Pigment Epithelium - metabolism ; Signal Transduction ; Stem cells ; Studies ; Time Factors ; Transcription ; Transcription factors ; Wnt Proteins - metabolism</subject><ispartof>PloS one, 2015-06, Vol.10 (6), p.e0130379-e0130379</ispartof><rights>2015 Choudhary et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://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>2015 Choudhary et al 2015 Choudhary et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-8205639c576ebe8e3479afd1731f1c1e30e26a470994c89bec7c465a974385b13</citedby><cites>FETCH-LOGICAL-c526t-8205639c576ebe8e3479afd1731f1c1e30e26a470994c89bec7c465a974385b13</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/PMC4488273/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488273/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26121260$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Choudhary, Parul</creatorcontrib><creatorcontrib>Dodsworth, Benjamin Thomas</creatorcontrib><creatorcontrib>Sidders, Ben</creatorcontrib><creatorcontrib>Gutteridge, Alex</creatorcontrib><creatorcontrib>Michaelides, Christos</creatorcontrib><creatorcontrib>Duckworth, Joshua Kane</creatorcontrib><creatorcontrib>Whiting, Paul John</creatorcontrib><creatorcontrib>Benn, Caroline Louise</creatorcontrib><title>A FOXM1 Dependent Mesenchymal-Epithelial Transition in Retinal Pigment Epithelium Cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The integrity of the epithelium is maintained by a complex but regulated interplay of processes that allow conversion of a proliferative state into a stably differentiated state. In this study, using human embryonic stem cell (hESC) derived Retinal Pigment Epithelium (RPE) cells as a model; we have investigated the molecular mechanisms that affect attainment of the epithelial phenotype. We demonstrate that RPE undergo a Mesenchymal-Epithelial Transition in culture before acquiring an epithelial phenotype in a FOXM1 dependent manner. We show that FOXM1 directly regulates proliferation of RPE through transcriptional control of cell cycle associated genes. Additionally, FOXM1 modulates expression of the signaling ligands BMP7 and Wnt5B which act reciprocally to enable epithelialization. This data uncovers a novel effect of FOXM1 dependent activities in contributing towards epithelial fate acquisition and furthers our understanding of the molecular regulators of a cell type that is currently being evaluated as a cell therapy.</description><subject>Bone Morphogenetic Protein 7 - metabolism</subject><subject>Cancer</subject><subject>Cell culture</subject><subject>Cell cycle</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Lineage</subject><subject>Cell Proliferation</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Epithelial Cells - pathology</subject><subject>Epithelial-Mesenchymal Transition</subject><subject>Epithelium</subject><subject>Forkhead Box Protein M1</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Kinases</subject><subject>Life assessment</subject><subject>Ligands</subject><subject>Macular degeneration</subject><subject>Mesenchyme</subject><subject>Metastasis</subject><subject>Molecular chains</subject><subject>Molecular modelling</subject><subject>Neurons - 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| subjects | Bone Morphogenetic Protein 7 - metabolism Cancer Cell culture Cell cycle Cell Differentiation - drug effects Cell Lineage Cell Proliferation Embryonic Stem Cells - cytology Epithelial Cells - pathology Epithelial-Mesenchymal Transition Epithelium Forkhead Box Protein M1 Forkhead Transcription Factors - metabolism Gene expression Gene Expression Profiling Gene Expression Regulation Homeostasis Humans Kinases Life assessment Ligands Macular degeneration Mesenchyme Metastasis Molecular chains Molecular modelling Neurons - metabolism Phase transitions Phenotype Phenotypes Proteins Regulators Retina Retinal pigment epithelium Retinal Pigment Epithelium - metabolism Signal Transduction Stem cells Studies Time Factors Transcription Transcription factors Wnt Proteins - metabolism |
| title | A FOXM1 Dependent Mesenchymal-Epithelial Transition in Retinal Pigment Epithelium Cells |
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