title: FolR1: a novel cell surface marker for isolating midbrain dopamine neural progenitors and nascent dopamine neurons.
abstract: Cell type-specific surface markers offer a powerful tool for purifying defined cell types for restorative therapies and drug screenings. Midbrain dopaminergic neurons (mesDA) are the nerve cells preferentially lost in the brains of Parkinson's disease patients. Clinical trials of transplantation of fetal neural precursors suggest that cell therapy may offer a cure for this devastating neurological disease. Many lines of preclinical studies demonstrate that neural progenitors committed to dopaminergic fate survive and integrate better than postmitotic DA neurons. We show that the folate-receptor 1 (FolR1), a GPI-anchored cell surface molecule, specifically marks mesDA neural progenitors and immature mesDA neurons. FolR1 expression superimposes with Lmx1a, a bona-fide mesDA lineage marker, during the active phase of mesDA neurogenesis from E9.5 to E14.5 during mouse development, as well as in ESC-derived mesDA lineage. FolR1(+) neural progenitors can be isolated by FACS or magnetic sorting (MAC) which give rise to dopamine neurons expressing TH and Pitx3, whilst FolR1 negative cells generate non-dopaminergic neurons and glia cells. This study identifies FolR1 as a new cell surface marker selectively expressed in mesDA progenitors in vivo and in vitro and that can be used to enrich in vitro differentiated TH neurons.
authors: Neuroscience and Mental Health Research Institute, School of Medicine and school of Bioscience, Cardiff University, Cardiff, CF24, 4HQ, UK.
authors: Nicole
authors: N
authors: Gennet
authors: Neuroscience and Mental Health Research Institute, School of Medicine and school of Bioscience, Cardiff University, Cardiff, CF24, 4HQ, UK.
authors: Claudia
authors: C
authors: Tamburini
authors: Neuroscience and Mental Health Research Institute, School of Medicine and school of Bioscience, Cardiff University, Cardiff, CF24, 4HQ, UK.
authors: Xinsheng
authors: X
authors: Nan
authors: Neuroscience and Mental Health Research Institute, School of Medicine and school of Bioscience, Cardiff University, Cardiff, CF24, 4HQ, UK.
authors: Meng
authors: M
authors: Li
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002469:Cell Separation / Q000379:methods; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000166:cytology / Q000378:metabolism*; D004622:Embryo, Mammalian; D058975:Folate Receptor 1 / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D058975:Folate Receptor 1; C520574:Folr1 protein, mouse; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C489692:Lmx1a protein, mouse; D014157:Transcription Factors; C433629:homeobox protein PITX3; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine