title: A FOXM1 Dependent Mesenchymal-Epithelial Transition in Retinal Pigment Epithelium Cells.
abstract: 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.
authors.affiliation: Neusentis, Pfizer Ltd, The Portway, Granta Park, Great Abington, Cambridge, United Kingdom.
authors.forename: Parul
authors.initials: P
authors.lastname: Choudhary
authors.affiliation: Neusentis, Pfizer Ltd, The Portway, Granta Park, Great Abington, Cambridge, United Kingdom.
authors.forename: Benjamin Thomas
authors.initials: BT
authors.lastname: Dodsworth
authors.affiliation: Neusentis, Pfizer Ltd, The Portway, Granta Park, Great Abington, Cambridge, United Kingdom.
authors.forename: Ben
authors.initials: B
authors.lastname: Sidders
authors.affiliation: Neusentis, Pfizer Ltd, The Portway, Granta Park, Great Abington, Cambridge, United Kingdom.
authors.forename: Alex
authors.initials: A
authors.lastname: Gutteridge
authors.affiliation: Neusentis, Pfizer Ltd, The Portway, Granta Park, Great Abington, Cambridge, United Kingdom.
authors.forename: Christos
authors.initials: C
authors.lastname: Michaelides
authors.affiliation: Neusentis, Pfizer Ltd, The Portway, Granta Park, Great Abington, Cambridge, United Kingdom.
authors.forename: Joshua Kane
authors.initials: JK
authors.lastname: Duckworth
authors.affiliation: Neusentis, Pfizer Ltd, The Portway, Granta Park, Great Abington, Cambridge, United Kingdom.
authors.forename: Paul John
authors.initials: PJ
authors.lastname: Whiting
authors.affiliation: Neusentis, Pfizer Ltd, The Portway, Granta Park, Great Abington, Cambridge, United Kingdom.
authors.forename: Caroline Louise
authors.initials: CL
authors.lastname: Benn
mesh_terms: D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D049109:Cell Proliferation; D053595:Embryonic Stem Cells / Q000166:cytology; D004847:Epithelial Cells / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008024:Ligands; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D055213:Retinal Pigment Epithelium / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D008024:Ligands; C435831:WNT5B protein, human; D051153:Wnt Proteins