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Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This study was supported by grants PI14/00302 and PI19/00593 from the Instituto de Salud Carlos III (Spain) with joint financing by FEDER funds from the European Union.

Analysis of institutional authors

Llaves-Lopez, AndreaAuthorRabaneda-Lombarte, NeusAuthorSola, CarmeAuthorSerratosa, JoanAuthorSaura, JosepCorresponding Author

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July 2, 2024
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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

Publicated to:Molecular Neurobiology. - 2024-06-20 (), DOI: 10.1007/s12035-024-04289-z

Authors: Llaves-López A; Micoli E; Belmonte-Mateos C; Aguilar G; Alba C; Marsal A; Pulido-Salgado M; Rabaneda-Lombarte N; Solà C; Serratosa J; Vidal-Taboada JM; Saura J

Affiliations

IDIBAPS, CSIC, Dept Neurosci & Expt Therapeut, IIBB, Barcelona, Catalonia, Spain - Author
Univ Barcelona, Inst Neurosci, Barcelona, Catalonia, Spain - Author
Univ Barcelona, Sch Med, Dept Biomed Sci, Biochem & Mol Biol Unit, Casanova 143, Barcelona 08036, Catalonia, Spain - Author
VHIR Vall dHebron Res Inst, Neurosci Dept, Peripheral Nervous Syst, Barcelona, Catalonia, Spain - Author

Abstract

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 alpha-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 beta (C/EBP beta) was achieved by small interfering RNA, resulting in the subsequent downregulation of proinflammatory genes. This supports the hypothesis that C/EBP beta 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.

Keywords

AstrocytesC/ebpbetC/ebpbetaCell cultureHealtIn vitro modelIn-vitro modelMicrogliaMonocyte-derivedNeuroinflammationNitric-oxide productionProgression

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Molecular Neurobiology due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2024 there are still no calculated indicators, but in 2023, it was in position 71/314, thus managing to position itself as a Q1 (Primer Cuartil), in the category Neurosciences.

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-08-08:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 9.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 14 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 14.5.
  • The number of mentions on the social network X (formerly Twitter): 1 (Altmetric).
  • The number of mentions in news outlets: 1 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Llaves López, Andrea) and Last Author (Saura Martí, Josep).

the author responsible for correspondence tasks has been Saura Martí, Josep.