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GPR17, a receptor transiently expressed on early OPCs, has emerged as a target to implement stroke repair through stimulation of OPC maturation. However, being GPR17 completely downregulated in myelin-producing oligodendrocytes, its actual role in determining the final fate of OPCs after cerebral ischemia is still uncertain. Here, to univocally define the spatiotemporal changes and final fate of GPR17-expressing OPCs, we induced ischemia by middle cerebral artery occlusion (MCAo) in reporter GPR17iCreER<jats:sup>T2<\/jats:sup>:CAG-eGreen florescent protein (GFP) mice, in which, upon tamoxifen treatment, cells expressing GPR17 become green and traceable for their entire life. Starting from 3 days and up to 2 weeks after MCAo, GFP<jats:sup>+<\/jats:sup> cells markedly accumulated in regions surrounding the ischemic lesion; several of them proliferated, as shown by co-labeling of the DNA synthesis marker 5-Bromo-2\u2032-deoxyuridine (BrdU). Almost all GFP<jats:sup>+<\/jats:sup>\/BrdU<jats:sup>+<\/jats:sup> cells expressed the OPC early marker neural\/glial antigen 2 (NG2), indicating that they were still precursors. Accumulation of GFP<jats:sup>+<\/jats:sup> cells was also because of OPC recruitment from surrounding areas, as suggested <jats:italic>in vivo<\/jats:italic> by acquisition of typical features of migrating OPCs, shown <jats:italic>in vitro<\/jats:italic> in presence of the chemoattractant PDGF-AA and confirmed by transplantation of GFP<jats:sup>+<\/jats:sup>-OPCs in wild-type MCAo mice. Eight weeks after MCAo, only some of these precociously recruited cells had undergone maturation as shown by NG2 loss and acquisition of mature myelinating markers like GSTpi. A pool of recruited GFP<jats:sup>+<\/jats:sup>-OPCs was kept at a precursor stage to likely make it available for further insults. Thus, very early after ischemia, GFP<jats:sup>+<\/jats:sup>-OPCs proliferate and migrate toward the lesion; however, most of these cells remain undifferentiated, suggesting functional roles other than myelination.<\/jats:p>","DOI":"10.1038\/cddis.2017.256","type":"journal-article","created":{"date-parts":[[2017,6,8]],"date-time":"2017-06-08T12:42:52Z","timestamp":1496925772000},"page":"e2871-e2871","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":101,"title":["The role of oligodendrocyte precursor cells expressing the GPR17 receptor in brain remodeling after stroke"],"prefix":"10.1038","volume":"8","author":[{"given":"Elisabetta","family":"Bonfanti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Gelosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Fumagalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leda","family":"Dimou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Vigan\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Tremoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Cimino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Sironi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria P","family":"Abbracchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,6,8]]},"reference":[{"key":"BFcddis2017256_CR1","doi-asserted-by":"publisher","first-page":"145","DOI":"10.3389\/fnins.2014.00145","volume":"8","author":"B El Waly","year":"2014","unstructured":"El Waly B, Macchi M, Cayre M, Durbec P . 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