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.
Highlights
Cell type-specific surface markers offer a powerful tool for purifying defined cell types for restorative therapies and drug screenings
One possible measure to guard safety is to transplant a committed dopaminergic cell population with defined molecular characteristics, that can be isolated by fluorescent activated cell sorter (FACS) or magnetic beads using a panel of cell surface markers[9]
From the expression study of E10.5 mouse embryos, folate-receptor 1 (FolR1) showed the most promising expression pattern in the ventral midbrain and we focused the studies on this marker subsequently
Summary
Cell type-specific surface markers offer a powerful tool for purifying defined cell types for restorative therapies and drug screenings. 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. Dopaminergic neurons derived from the ventral mesencephalon (mesDA) are the cells preferentially lost in the brains of Parkinson’s disease patients. Proof of principle has been provided that pluripotent stem cell (PSC)-derived mesDA neural progenitors are able to survive and differentiate into mature dopamine neurons in animal models of Parkinson’s disease and exhibit some functional characteristics[1,2], promising hope for the development of cell transplantation therapy for treating Parkinson’s disease. Notwithstanding the significant development of new robust small molecule based mesDA differentiation protocols[1,7,8], PSC-derived dopaminergic cultures still contain other cellular identities such as non-DA neuronal subtypes, non-neural cells and undifferentiated intermediates. Correspondence and requests for materials should be addressed to M.L. (email: lim26@ cf.ac.uk) www.nature.com/scientificreports/
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call