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  1. Article: In silico-in vitro

    Timmerman, Raissa / Zuiderwijk-Sick, Ella Alwine / Baron, Wia / Bajramovic, Jeffrey John

    Frontiers in cellular neuroscience

    2023  Volume 17, Page(s) 1178504

    Abstract: Microglia are the resident macrophages of the central nervous system (CNS) and play a key role in CNS development, homeostasis, and disease. ... ...

    Abstract Microglia are the resident macrophages of the central nervous system (CNS) and play a key role in CNS development, homeostasis, and disease. Good
    Language English
    Publishing date 2023-06-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2023.1178504
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: In vitro

    Sharaf, Ahmed / Timmerman, Raissa / Bajramovic, Jeffrey / Accardo, Angelo

    Neural regeneration research

    2022  Volume 18, Issue 8, Page(s) 1709–1710

    Language English
    Publishing date 2022-11-26
    Publishing country India
    Document type Journal Article
    ZDB-ID 2388460-5
    ISSN 1876-7958 ; 1673-5374
    ISSN (online) 1876-7958
    ISSN 1673-5374
    DOI 10.4103/1673-5374.363828
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: P2Y6 receptor-mediated signaling amplifies TLR-induced pro-inflammatory responses in microglia.

    Timmerman, Raissa / Zuiderwijk-Sick, Ella A / Bajramovic, Jeffrey J

    Frontiers in immunology

    2022  Volume 13, Page(s) 967951

    Abstract: TLR-induced signaling initiates inflammatory responses in cells of the innate immune system. These responses are amongst others characterized by the secretion of high levels of pro-inflammatory cytokines, which are tightly regulated and adapted to the ... ...

    Abstract TLR-induced signaling initiates inflammatory responses in cells of the innate immune system. These responses are amongst others characterized by the secretion of high levels of pro-inflammatory cytokines, which are tightly regulated and adapted to the microenvironment. Purinergic receptors are powerful modulators of TLR-induced responses, and we here characterized the effects of P2Y6 receptor (P2RY6)-mediated signaling on TLR responses of rhesus macaque primary bone marrow-derived macrophages (BMDM) and microglia, using the selective P2RY6 antagonist MRS2578. We demonstrate that P2RY6-mediated signaling enhances the levels of TLR-induced pro-inflammatory cytokines in microglia in particular. TLR1, 2, 4, 5 and 8-induced responses were all enhanced in microglia, whereas such effects were much less pronounced in BMDM from the same donors. Transcriptome analysis revealed that the overall contribution of P2RY6-mediated signaling to TLR-induced responses in microglia leads to an amplification of pro-inflammatory responses. Detailed target gene analysis predicts that P2RY6-mediated signaling regulates the expression of these genes
    MeSH term(s) Animals ; Cytokines/metabolism ; Heat-Shock Proteins/metabolism ; Macaca mulatta ; Microglia ; NF-kappa B/metabolism ; Receptors, Purinergic P2 ; Toll-Like Receptor 1/metabolism
    Chemical Substances Cytokines ; Heat-Shock Proteins ; NF-kappa B ; Receptors, Purinergic P2 ; Toll-Like Receptor 1 ; purinoceptor P2Y6
    Language English
    Publishing date 2022-09-20
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.967951
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Two-Photon Polymerization of 2.5D and 3D Microstructures Fostering a Ramified Resting Phenotype in Primary Microglia.

    Sharaf, Ahmed / Roos, Brian / Timmerman, Raissa / Kremers, Gert-Jan / Bajramovic, Jeffrey John / Accardo, Angelo

    Frontiers in bioengineering and biotechnology

    2022  Volume 10, Page(s) 926642

    Abstract: Microglia are the resident macrophages of the central nervous system and contribute to maintaining brain's homeostasis. Current 2D "petri-dish" ...

    Abstract Microglia are the resident macrophages of the central nervous system and contribute to maintaining brain's homeostasis. Current 2D "petri-dish"
    Language English
    Publishing date 2022-07-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2719493-0
    ISSN 2296-4185
    ISSN 2296-4185
    DOI 10.3389/fbioe.2022.926642
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: An Overview of

    Timmerman, Raissa / Burm, Saskia M / Bajramovic, Jeffrey J

    Frontiers in cellular neuroscience

    2018  Volume 12, Page(s) 242

    Abstract: Neuroinflammation is a common feature in neurodegenerative diseases and strategies to modulate neuroinflammatory processes are increasingly considered as therapeutic options. In such strategies, glia cells rather than neurons represent the cellular ... ...

    Abstract Neuroinflammation is a common feature in neurodegenerative diseases and strategies to modulate neuroinflammatory processes are increasingly considered as therapeutic options. In such strategies, glia cells rather than neurons represent the cellular targets. Microglia, the resident macrophages of the central nervous system, are principal players in neuroinflammation and detailed cellular biological knowledge of this particular cell type is therefore of pivotal importance. The last decade has shed new light on the origin, characteristics and functions of microglia, underlining the need for specific
    Language English
    Publishing date 2018-08-06
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2018.00242
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: FoxO3 Modulates Circadian Rhythms in Neural Stem Cells.

    Draijer, Swip / Timmerman, Raissa / Pannekeet, Jesse / van Harten, Alexandra / Farshadi, Elham Aida / Kemmer, Julius / van Gilst, Demy / Chaves, Inês / Hoekman, Marco F M

    International journal of molecular sciences

    2023  Volume 24, Issue 17

    Abstract: Both FoxO transcription factors and the circadian clock act on the interface of metabolism and cell cycle regulation and are important regulators of cellular stress and stem cell homeostasis. Importantly, FoxO3 preserves the adult neural stem cell ... ...

    Abstract Both FoxO transcription factors and the circadian clock act on the interface of metabolism and cell cycle regulation and are important regulators of cellular stress and stem cell homeostasis. Importantly, FoxO3 preserves the adult neural stem cell population by regulating cell cycle and cellular metabolism and has been shown to regulate circadian rhythms in the liver. However, whether FoxO3 is a regulator of circadian rhythms in neural stem cells remains unknown. Here, we show that loss of FoxO3 disrupts circadian rhythmicity in cultures of neural stem cells, an effect that is mediated via regulation of
    MeSH term(s) Animals ; Mice ; Cell Cycle ; Cell Division ; Circadian Clocks/genetics ; Circadian Rhythm/genetics ; Neural Stem Cells ; Forkhead Box Protein O3/genetics ; Forkhead Box Protein O3/physiology
    Chemical Substances Forkhead Box Protein O3 ; FoxO3 protein, mouse
    Language English
    Publishing date 2023-09-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms241713662
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Exposure of Microglia to Interleukin-4 Represses NF-κB-Dependent Transcription of Toll-Like Receptor-Induced Cytokines.

    Zuiderwijk-Sick, Ella A / van der Putten, Céline / Timmerman, Raissa / Veth, Jennifer / Pasini, Erica M / van Straalen, Linda / van der Valk, Paul / Amor, Sandra / Bajramovic, Jeffrey J

    Frontiers in immunology

    2021  Volume 12, Page(s) 771453

    Abstract: Interleukin (IL)-4 is a cytokine that affects both adaptive and innate immune responses. In the central nervous system, microglia express IL-4 receptors and it has been described that IL-4-exposed microglia acquire anti-inflammatory properties. We here ... ...

    Abstract Interleukin (IL)-4 is a cytokine that affects both adaptive and innate immune responses. In the central nervous system, microglia express IL-4 receptors and it has been described that IL-4-exposed microglia acquire anti-inflammatory properties. We here demonstrate that IL-4 exposure induces changes in the cell surface protein expression profile of primary rhesus macaque microglia and enhances their potential to induce proliferation of T cells with a regulatory signature. Moreover, we show that Toll like receptor (TLR)-induced cytokine production is broadly impaired in IL-4-exposed microglia at the transcriptional level. IL-4 type 2 receptor-mediated signaling is shown to be crucial for the inhibition of microglial innate immune responses. TLR-induced nuclear translocalization of NF-κB appeared intact, and we found no evidence for epigenetic modulation of target genes. By contrast, nuclear extracts from IL-4-exposed microglia contained significantly less NF-κB capable of binding to its DNA consensus site. Further identification of the molecular mechanisms that underlie the inhibition of TLR-induced responses in IL-4-exposed microglia may aid the design of strategies that aim to modulate innate immune responses in the brain, for example in gliomas.
    MeSH term(s) Animals ; Cell Proliferation ; Cells, Cultured ; Cytokines/immunology ; Female ; Histone Deacetylases/genetics ; Lipopolysaccharides/pharmacology ; Macaca mulatta ; Male ; Microglia/immunology ; NF-kappa B/immunology ; T-Lymphocytes/immunology ; Toll-Like Receptors/immunology ; Transcription, Genetic
    Chemical Substances Cytokines ; Lipopolysaccharides ; NF-kappa B ; Toll-Like Receptors ; Histone Deacetylases (EC 3.5.1.98)
    Language English
    Publishing date 2021-11-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.771453
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Transcriptome analysis reveals the contribution of oligodendrocyte and radial glia-derived cues for maintenance of microglia identity.

    Timmerman, Raissa / Zuiderwijk-Sick, Ella A / Oosterhof, Nynke / 't Jong, Anke E J / Veth, Jennifer / Burm, Saskia M / van Ham, Tjakko J / Bajramovic, Jeffrey J

    Glia

    2021  Volume 70, Issue 4, Page(s) 728–747

    Abstract: Microglia are increasingly being recognized as druggable targets in neurodegenerative disorders, and good in vitro models are crucial to address cell biological questions. Major challenges are to recapitulate the complex microglial morphology and their ... ...

    Abstract Microglia are increasingly being recognized as druggable targets in neurodegenerative disorders, and good in vitro models are crucial to address cell biological questions. Major challenges are to recapitulate the complex microglial morphology and their in vivo transcriptome. We have therefore exposed primary microglia from adult rhesus macaques to a variety of different culture conditions including exposure to soluble factors as M-CSF, IL-34, and TGF-β as well as serum replacement approaches, and compared their morphologies and transcriptomes to those of mature, homeostatic in vivo microglia. This enabled us to develop a new, partially serum-free, monoculture protocol, that yields high numbers of ramified cells. We also demonstrate that exposure of adult microglia to M-CSF or IL-34 induces similar transcriptomes, and that exposure to TGF-β has much less pronounced effects than it does on rodent microglia. However, regardless of culture conditions, the transcriptomes of in vitro and in vivo microglia remained substantially different. Analysis of differentially expressed genes inspired us to perform 3D-spherical coculture experiments of microglia with oligodendrocytes and radial glia. In such spheres, microglia signature genes were strongly induced, even in the absence of neurons and astrocytes. These data reveal a novel role for oligodendrocyte and radial glia-derived cues in the maintenance of microglial identity, providing new anchor points to study microglia in health and disease.
    MeSH term(s) Animals ; Cues ; Ependymoglial Cells ; Gene Expression Profiling ; Macaca mulatta ; Microglia ; Oligodendroglia ; Transcriptome
    Language English
    Publishing date 2021-12-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 639414-0
    ISSN 1098-1136 ; 0894-1491
    ISSN (online) 1098-1136
    ISSN 0894-1491
    DOI 10.1002/glia.24136
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2345: Show issues Location:
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  9. Article ; Online: Rapid and efficient induction of functional astrocytes from human pluripotent stem cells.

    Canals, Isaac / Ginisty, Aurélie / Quist, Ella / Timmerman, Raissa / Fritze, Jonas / Miskinyte, Giedre / Monni, Emanuela / Hansen, Marita G / Hidalgo, Isabel / Bryder, David / Bengzon, Johan / Ahlenius, Henrik

    Nature methods

    2018  Volume 15, Issue 9, Page(s) 693–696

    Abstract: The derivation of astrocytes from human pluripotent stem cells is currently slow and inefficient. We demonstrate that overexpression of the transcription factors SOX9 and NFIB in human pluripotent stem cells rapidly and efficiently yields homogeneous ... ...

    Abstract The derivation of astrocytes from human pluripotent stem cells is currently slow and inefficient. We demonstrate that overexpression of the transcription factors SOX9 and NFIB in human pluripotent stem cells rapidly and efficiently yields homogeneous populations of induced astrocytes. In our study these cells exhibited molecular and functional properties resembling those of adult human astrocytes and were deemed suitable for disease modeling. Our method provides new possibilities for the study of human astrocytes in health and disease.
    MeSH term(s) Astrocytes/cytology ; Cell Differentiation ; Humans ; NFI Transcription Factors/metabolism ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/metabolism ; SOX9 Transcription Factor/metabolism
    Chemical Substances NFI Transcription Factors ; NFIB protein, human ; SOX9 Transcription Factor ; SOX9 protein, human
    Language English
    Publishing date 2018-08-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2169522-2
    ISSN 1548-7105 ; 1548-7091
    ISSN (online) 1548-7105
    ISSN 1548-7091
    DOI 10.1038/s41592-018-0103-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Author Correction: Rapid and efficient induction of functional astrocytes from human pluripotent stem cells.

    Canals, Isaac / Ginisty, Aurélie / Quist, Ella / Timmerman, Raissa / Fritze, Jonas / Miskinyte, Giedre / Monni, Emanuela / Hansen, Marita G / Hidalgo, Isabel / Bryder, David / Bengzon, Johan / Ahlenius, Henrik

    Nature methods

    2018  Volume 16, Issue 1, Page(s) 134

    Abstract: In the version of Supplementary Fig. 1 originally published with this paper, some images in panel e were accidental duplicates of images in panel b. This error has been corrected in the online integrated supplementary information and in the Supplementary ...

    Abstract In the version of Supplementary Fig. 1 originally published with this paper, some images in panel e were accidental duplicates of images in panel b. This error has been corrected in the online integrated supplementary information and in the Supplementary Information PDF.
    Language English
    Publishing date 2018-12-04
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ZDB-ID 2169522-2
    ISSN 1548-7105 ; 1548-7091
    ISSN (online) 1548-7105
    ISSN 1548-7091
    DOI 10.1038/s41592-018-0264-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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