Title | Circulating platelets modulate oligodendrocyte progenitor cell differentiation during remyelination |
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Type | Journal article |
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Authors | Philp, Amber R., Reyes, C., Mansilla, Josselyne, Sharma, Amar, Zhao, Chao, Valenzuela-Krugmann, C., Rawji, K., Gonzalez Martinez, Ginez A, Dimas, Penelope, Hinrichsen, Bryan, Ulloa-Leal, César, Waller, Amie K., Bessa de Sousa, Diana M, Castro, Maite A., Aigner, Ludwig, Ehrenfeld, Pamela, Silva, M., Kazanis, Ilias, Ghevaert, Cedric, Franklin, Robin J.M. and Rivera, F. |
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Abstract | Revealing unknown cues that regulate oligodendrocyte progenitor cell (OPC) function in remyelination is important to optimise the development of regenerative therapies for multiple sclerosis (MS). Platelets are present in chronic non-remyelinated lesions of MS and an increase in circulating platelets has been described in experimental autoimmune encephalomyelitis (EAE) mice, an animal model for MS. However, the contribution of platelets to remyelination remains unexplored. Here we show platelet aggregation in proximity to OPCs in areas of experimental demyelination. Partial depletion of circulating platelets impaired OPC differentiation and remyelination, without altering blood-brain barrier stability and neuroinflammation. Transient exposure to platelets enhanced OPC differentiation in vitro, whereas sustained exposure suppressed this effect. In a mouse model of thrombocytosis (Calr+/-), there was a sustained increase in platelet aggregation together with a reduction of newly-generated oligodendrocytes following toxin-induced demyelination. These findings reveal a complex bimodal contribution of platelet to remyelination and provide insights into remyelination failure in MS. |
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Article number | RP91757 |
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Journal | eLife |
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Journal citation | 12 |
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ISSN | 2050-084X |
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Year | 2024 |
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Publisher | eLife Sciences Publications, Ltd |
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Publisher's version | License CC BY 4.0 File Access Level Open (open metadata and files) |
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Digital Object Identifier (DOI) | https://doi.org/10.7554/elife.91757 |
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PubMed ID | 39163103 |
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Publication dates |
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Published online | 20 Aug 2024 |
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Project | Fondecyt Regular Number 1201706 and Number 1161787 |
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| PCI Program Grant Number REDES170233 |
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| National Doctoral Fellowship Number 21170732 |
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| Fondecyt Regular Number 1201635 |
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Funder | Agencia Nacional de Investigación y Desarrollo |
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| Agencia Nacional de Investigación y Desarrollo |
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| Agencia Nacional de Investigación y Desarrollo |
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| Agencia Nacional de Investigación y Desarrollo |
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| Agencia Nacional de Investigación y Desarrollo |
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| Agencia Nacional de Investigación y Desarrollo |
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| Agencia Nacional de Investigación y Desarrollo |
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License | http://creativecommons.org/licenses/by/4.0/ |
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