Microglia modulate proliferation, neurite generation and differentiation of human neural progenitor cells
Microglia, the primary immune cells of the brain, significantly influence the fate of neurons after neural damage. Depending on the local environment, they exhibit a wide range of phenotypes, including patrolling (naïve), proinflammatory, and anti-inflammatory characteristics, which greatly affects...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.997028/full |
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| author | Julianna Lilienberg Julianna Lilienberg Ágota Apáti János M. Réthelyi János M. Réthelyi László Homolya |
| author_facet | Julianna Lilienberg Julianna Lilienberg Ágota Apáti János M. Réthelyi János M. Réthelyi László Homolya |
| author_sort | Julianna Lilienberg |
| collection | DOAJ |
| description | Microglia, the primary immune cells of the brain, significantly influence the fate of neurons after neural damage. Depending on the local environment, they exhibit a wide range of phenotypes, including patrolling (naïve), proinflammatory, and anti-inflammatory characteristics, which greatly affects neurotoxicity. Despite the fact that neural progenitor cells (NPCs) and hippocampal neurons represent cell populations, which play pivotal role in neural regeneration, interaction between microglia and these cell types is poorly studied. In the present work, we investigated how microglial cells affect the proliferation and neurite outgrowth of human stem cell-derived NPCs, and how microglia stimulation with proinflammatory or anti-inflammatory agents modulates this interaction. We found that naïve microglia slightly diminish NPC proliferation and have no effect on neurite outgrowth. In contrast, proinflammatory stimulated microglia promote both proliferation and neurite generation, whereas microglia stimulated with anti-inflammatory cytokines augment neurite outgrowth leaving NPC proliferation unaffected. We also studied how microglia influence neurite development and differentiation of hippocampal dentate gyrus granule cells differentiated from NPCs. We found that proinflammatory stimulated microglia inhibit axonal development but facilitate dendrite generation in these differentiating neurons. Our results elucidate a fine-tuned modulatory effect of microglial cells on cell types crucial for neural regeneration, opening perspectives for novel regenerative therapeutic interventions. |
| first_indexed | 2024-04-13T23:33:16Z |
| format | Article |
| id | doaj.art-51edf91c7d484bc58a643f06f51bab9f |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-13T23:33:16Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-51edf91c7d484bc58a643f06f51bab9f2022-12-22T02:24:49ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-10-011010.3389/fcell.2022.997028997028Microglia modulate proliferation, neurite generation and differentiation of human neural progenitor cellsJulianna Lilienberg0Julianna Lilienberg1Ágota Apáti2János M. Réthelyi3János M. Réthelyi4László Homolya5Institute of Enzymology, Research Centre for Natural Sciences, Budapest, HungaryDoctoral School of Biology, Institute of Biology, ELTE Eötvös Loránd University, Budapest, HungaryInstitute of Enzymology, Research Centre for Natural Sciences, Budapest, HungaryMolecular Psychiatry and in vitro Disease Modelling Research Group, National Brain Research Project, Hungarian Academy of Sciences and Semmelweis University, Budapest, HungaryDepartment of Psychiatry and Psychotherapy, Semmelweis University, Budapest, HungaryInstitute of Enzymology, Research Centre for Natural Sciences, Budapest, HungaryMicroglia, the primary immune cells of the brain, significantly influence the fate of neurons after neural damage. Depending on the local environment, they exhibit a wide range of phenotypes, including patrolling (naïve), proinflammatory, and anti-inflammatory characteristics, which greatly affects neurotoxicity. Despite the fact that neural progenitor cells (NPCs) and hippocampal neurons represent cell populations, which play pivotal role in neural regeneration, interaction between microglia and these cell types is poorly studied. In the present work, we investigated how microglial cells affect the proliferation and neurite outgrowth of human stem cell-derived NPCs, and how microglia stimulation with proinflammatory or anti-inflammatory agents modulates this interaction. We found that naïve microglia slightly diminish NPC proliferation and have no effect on neurite outgrowth. In contrast, proinflammatory stimulated microglia promote both proliferation and neurite generation, whereas microglia stimulated with anti-inflammatory cytokines augment neurite outgrowth leaving NPC proliferation unaffected. We also studied how microglia influence neurite development and differentiation of hippocampal dentate gyrus granule cells differentiated from NPCs. We found that proinflammatory stimulated microglia inhibit axonal development but facilitate dendrite generation in these differentiating neurons. Our results elucidate a fine-tuned modulatory effect of microglial cells on cell types crucial for neural regeneration, opening perspectives for novel regenerative therapeutic interventions.https://www.frontiersin.org/articles/10.3389/fcell.2022.997028/fullhuman neural progenitor cellmicroglianeuriteneural regenerationneuronal polarizationmicroglia polarization |
| spellingShingle | Julianna Lilienberg Julianna Lilienberg Ágota Apáti János M. Réthelyi János M. Réthelyi László Homolya Microglia modulate proliferation, neurite generation and differentiation of human neural progenitor cells Frontiers in Cell and Developmental Biology human neural progenitor cell microglia neurite neural regeneration neuronal polarization microglia polarization |
| title | Microglia modulate proliferation, neurite generation and differentiation of human neural progenitor cells |
| title_full | Microglia modulate proliferation, neurite generation and differentiation of human neural progenitor cells |
| title_fullStr | Microglia modulate proliferation, neurite generation and differentiation of human neural progenitor cells |
| title_full_unstemmed | Microglia modulate proliferation, neurite generation and differentiation of human neural progenitor cells |
| title_short | Microglia modulate proliferation, neurite generation and differentiation of human neural progenitor cells |
| title_sort | microglia modulate proliferation neurite generation and differentiation of human neural progenitor cells |
| topic | human neural progenitor cell microglia neurite neural regeneration neuronal polarization microglia polarization |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.997028/full |
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