Human microglia-like cells differentiated from monocytes with GM-CSF and IL-34 show phagocytosis of α-synuclein aggregates and C/EBPβ-dependent proinflammatory activation

Microglia, the main resident immune cells in the central nervous system, are implicated in the pathogenesis of various neurological disorders. Much of our knowledge on microglial biology was obtained using rodent microglial cultures. To understand the role of microglia in human disease, reliable in...

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Autores: Llaves López, Andrea, Micoli, Elia, Belmonte Mateos, Carla, Aguilar, Gerard, Alba, Clara, Marsal, Anais, Pulido Salgado, Marta, Rabaneda Lombarte, Neus, Solà i Subirana, Carme, Serratosa i Serdà, Joan, Vidal Taboada, José Manuel, Saura Martí, Josep
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/226838
Acceso en línea:https://hdl.handle.net/2445/226838
Access Level:acceso abierto
Palabra clave:Patologia cel·lular
Micròglia
Neuroimmunologia
Cellular pathology
Microglia
Neuroimmunology
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spelling Human microglia-like cells differentiated from monocytes with GM-CSF and IL-34 show phagocytosis of α-synuclein aggregates and C/EBPβ-dependent proinflammatory activationLlaves López, AndreaMicoli, EliaBelmonte Mateos, CarlaAguilar, GerardAlba, ClaraMarsal, AnaisPulido Salgado, MartaRabaneda Lombarte, NeusSolà i Subirana, CarmeSerratosa i Serdà, JoanVidal Taboada, José ManuelSaura Martí, JosepPatologia cel·lularMicrògliaNeuroimmunologiaCellular pathologyMicrogliaNeuroimmunologyMicroglia, the main resident immune cells in the central nervous system, are implicated in the pathogenesis of various neurological disorders. Much of our knowledge on microglial biology was obtained using rodent microglial cultures. To understand the role of microglia in human disease, reliable in vitro models of human microglia are necessary. Monocyte-derived microglia-like cells (MDMi) are a promising approach. This study aimed to characterize MDMi cells generated from adult human monocytes using granulocyte–macrophage colony-stimulating factor and interleukin-34. To this end, 49 independent cultures of MDMI were prepared, and various methodological and functional studies were performed. We show that with this protocol, adult human monocytes develop into microglia-like cells, a coating is unnecessary, and high cell density seeding is preferable. When compared to monocytes, MDMi upregulate the expression of many, but not all, microglial markers, indicating that, although these cells display a microglia-like phenotype, they cannot be considered bona fide human microglia. At the functional level, MDMi phagocytose α-synuclein aggregates and responds to lipopolysaccharide (LPS) by nuclear translocation of the transcription factor nuclear factor-kappaB (NFkappaB) and the upregulation of proinflammatory genes. Finally, a long-lasting silencing of the transcription factor CCAAT/enhancer protein β (C/EBPβ) was achieved by small interfering RNA, resulting in the subsequent downregulation of proinflammatory genes. This supports the hypothesis that C/EBPβ plays a key role in proinflammatory gene program activation in human microglia. Altogether, this study sheds new light on the properties of MDMi cells and supports these cells as a promising in vitro model for studying adult human microglia–like cells.Springer Nature2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/226838Articles publicats en revistes (Biomedicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1007/s12035-024-04289-zMolecular Neurobiology, 2025, vol. 62, p. 756-772https://doi.org/10.1007/s12035-024-04289-zcc-by (c) Llaves López, Andrea et al., 2024http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2268382026-05-27T06:46:51Z
dc.title.none.fl_str_mv Human microglia-like cells differentiated from monocytes with GM-CSF and IL-34 show phagocytosis of α-synuclein aggregates and C/EBPβ-dependent proinflammatory activation
title Human microglia-like cells differentiated from monocytes with GM-CSF and IL-34 show phagocytosis of α-synuclein aggregates and C/EBPβ-dependent proinflammatory activation
spellingShingle Human microglia-like cells differentiated from monocytes with GM-CSF and IL-34 show phagocytosis of α-synuclein aggregates and C/EBPβ-dependent proinflammatory activation
Llaves López, Andrea
Patologia cel·lular
Micròglia
Neuroimmunologia
Cellular pathology
Microglia
Neuroimmunology
title_short Human microglia-like cells differentiated from monocytes with GM-CSF and IL-34 show phagocytosis of α-synuclein aggregates and C/EBPβ-dependent proinflammatory activation
title_full Human microglia-like cells differentiated from monocytes with GM-CSF and IL-34 show phagocytosis of α-synuclein aggregates and C/EBPβ-dependent proinflammatory activation
title_fullStr Human microglia-like cells differentiated from monocytes with GM-CSF and IL-34 show phagocytosis of α-synuclein aggregates and C/EBPβ-dependent proinflammatory activation
title_full_unstemmed Human microglia-like cells differentiated from monocytes with GM-CSF and IL-34 show phagocytosis of α-synuclein aggregates and C/EBPβ-dependent proinflammatory activation
title_sort Human microglia-like cells differentiated from monocytes with GM-CSF and IL-34 show phagocytosis of α-synuclein aggregates and C/EBPβ-dependent proinflammatory activation
dc.creator.none.fl_str_mv Llaves López, Andrea
Micoli, Elia
Belmonte Mateos, Carla
Aguilar, Gerard
Alba, Clara
Marsal, Anais
Pulido Salgado, Marta
Rabaneda Lombarte, Neus
Solà i Subirana, Carme
Serratosa i Serdà, Joan
Vidal Taboada, José Manuel
Saura Martí, Josep
author Llaves López, Andrea
author_facet Llaves López, Andrea
Micoli, Elia
Belmonte Mateos, Carla
Aguilar, Gerard
Alba, Clara
Marsal, Anais
Pulido Salgado, Marta
Rabaneda Lombarte, Neus
Solà i Subirana, Carme
Serratosa i Serdà, Joan
Vidal Taboada, José Manuel
Saura Martí, Josep
author_role author
author2 Micoli, Elia
Belmonte Mateos, Carla
Aguilar, Gerard
Alba, Clara
Marsal, Anais
Pulido Salgado, Marta
Rabaneda Lombarte, Neus
Solà i Subirana, Carme
Serratosa i Serdà, Joan
Vidal Taboada, José Manuel
Saura Martí, Josep
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Patologia cel·lular
Micròglia
Neuroimmunologia
Cellular pathology
Microglia
Neuroimmunology
topic Patologia cel·lular
Micròglia
Neuroimmunologia
Cellular pathology
Microglia
Neuroimmunology
description Microglia, the main resident immune cells in the central nervous system, are implicated in the pathogenesis of various neurological disorders. Much of our knowledge on microglial biology was obtained using rodent microglial cultures. To understand the role of microglia in human disease, reliable in vitro models of human microglia are necessary. Monocyte-derived microglia-like cells (MDMi) are a promising approach. This study aimed to characterize MDMi cells generated from adult human monocytes using granulocyte–macrophage colony-stimulating factor and interleukin-34. To this end, 49 independent cultures of MDMI were prepared, and various methodological and functional studies were performed. We show that with this protocol, adult human monocytes develop into microglia-like cells, a coating is unnecessary, and high cell density seeding is preferable. When compared to monocytes, MDMi upregulate the expression of many, but not all, microglial markers, indicating that, although these cells display a microglia-like phenotype, they cannot be considered bona fide human microglia. At the functional level, MDMi phagocytose α-synuclein aggregates and responds to lipopolysaccharide (LPS) by nuclear translocation of the transcription factor nuclear factor-kappaB (NFkappaB) and the upregulation of proinflammatory genes. Finally, a long-lasting silencing of the transcription factor CCAAT/enhancer protein β (C/EBPβ) was achieved by small interfering RNA, resulting in the subsequent downregulation of proinflammatory genes. This supports the hypothesis that C/EBPβ plays a key role in proinflammatory gene program activation in human microglia. Altogether, this study sheds new light on the properties of MDMi cells and supports these cells as a promising in vitro model for studying adult human microglia–like cells.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/226838
url https://hdl.handle.net/2445/226838
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1007/s12035-024-04289-z
Molecular Neurobiology, 2025, vol. 62, p. 756-772
https://doi.org/10.1007/s12035-024-04289-z
dc.rights.none.fl_str_mv cc-by (c) Llaves López, Andrea et al., 2024
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Llaves López, Andrea et al., 2024
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv Articles publicats en revistes (Biomedicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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