microRNA-132 regulates gene expression programs involved in microglial homeostasis
Summary: microRNA-132 (miR-132), a known neuronal regulator, is one of the most robustly downregulated microRNAs (miRNAs) in the brain of Alzheimer’s disease (AD) patients. Increasing miR-132 in AD mouse brain ameliorates amyloid and Tau pathologies, and also restores adult hippocampal neurogenesis...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223009069 |
| _version_ | 1827943906427273216 |
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| author | Hannah Walgrave Amber Penning Giorgia Tosoni Sarah Snoeck Kristofer Davie Emma Davis Leen Wolfs Annerieke Sierksma Mayte Mars Taofeng Bu Nicola Thrupp Lujia Zhou Diederik Moechars Renzo Mancuso Mark Fiers Andrew J.M. Howden Bart De Strooper Evgenia Salta |
| author_facet | Hannah Walgrave Amber Penning Giorgia Tosoni Sarah Snoeck Kristofer Davie Emma Davis Leen Wolfs Annerieke Sierksma Mayte Mars Taofeng Bu Nicola Thrupp Lujia Zhou Diederik Moechars Renzo Mancuso Mark Fiers Andrew J.M. Howden Bart De Strooper Evgenia Salta |
| author_sort | Hannah Walgrave |
| collection | DOAJ |
| description | Summary: microRNA-132 (miR-132), a known neuronal regulator, is one of the most robustly downregulated microRNAs (miRNAs) in the brain of Alzheimer’s disease (AD) patients. Increasing miR-132 in AD mouse brain ameliorates amyloid and Tau pathologies, and also restores adult hippocampal neurogenesis and memory deficits. However, the functional pleiotropy of miRNAs requires in-depth analysis of the effects of miR-132 supplementation before it can be moved forward for AD therapy. We employ here miR-132 loss- and gain-of-function approaches using single-cell transcriptomics, proteomics, and in silico AGO-CLIP datasets to identify molecular pathways targeted by miR-132 in mouse hippocampus. We find that miR-132 modulation significantly affects the transition of microglia from a disease-associated to a homeostatic cell state. We confirm the regulatory role of miR-132 in shifting microglial cell states using human microglial cultures derived from induced pluripotent stem cells. |
| first_indexed | 2024-03-13T10:22:24Z |
| format | Article |
| id | doaj.art-fb4068bec1c2405a988aa5fa7009aa7c |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-13T10:22:24Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-fb4068bec1c2405a988aa5fa7009aa7c2023-05-20T04:30:42ZengElsevieriScience2589-00422023-06-01266106829microRNA-132 regulates gene expression programs involved in microglial homeostasisHannah Walgrave0Amber Penning1Giorgia Tosoni2Sarah Snoeck3Kristofer Davie4Emma Davis5Leen Wolfs6Annerieke Sierksma7Mayte Mars8Taofeng Bu9Nicola Thrupp10Lujia Zhou11Diederik Moechars12Renzo Mancuso13Mark Fiers14Andrew J.M. Howden15Bart De Strooper16Evgenia Salta17VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; KU Leuven, Department of Neurosciences, Leuven Brain Institute (LBI), 3000 Leuven, BelgiumNetherlands Institute for Neuroscience, 1105 BA Amsterdam, the NetherlandsNetherlands Institute for Neuroscience, 1105 BA Amsterdam, the NetherlandsNetherlands Institute for Neuroscience, 1105 BA Amsterdam, the NetherlandsVIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; VIB-KU Leuven Center for Brain & Disease Research, Bioinformatics Core Facility, 3000 Leuven, BelgiumUK Dementia Research Institute at UCL, London WC1E 6BT, UKVIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; KU Leuven, Department of Neurosciences, Leuven Brain Institute (LBI), 3000 Leuven, BelgiumVIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; KU Leuven, Department of Neurosciences, Leuven Brain Institute (LBI), 3000 Leuven, BelgiumNetherlands Institute for Neuroscience, 1105 BA Amsterdam, the NetherlandsVIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; KU Leuven, Department of Neurosciences, Leuven Brain Institute (LBI), 3000 Leuven, BelgiumVIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; KU Leuven, Department of Neurosciences, Leuven Brain Institute (LBI), 3000 Leuven, BelgiumDiscovery Neuroscience, Janssen Research and Development, Division of Janssen Pharmaceutica NV, 2340 Beerse, BelgiumDiscovery Neuroscience, Janssen Research and Development, Division of Janssen Pharmaceutica NV, 2340 Beerse, BelgiumMicroglia and Inflammation in Neurological Disorders (MIND) Lab, VIB Center for Molecular Neurology, VIB, 2610 Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, 2610 Antwerp, BelgiumVIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; KU Leuven, Department of Neurosciences, Leuven Brain Institute (LBI), 3000 Leuven, BelgiumUK Dementia Research Institute, University of Dundee, Dundee DD1 4HN, UKVIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; KU Leuven, Department of Neurosciences, Leuven Brain Institute (LBI), 3000 Leuven, Belgium; UK Dementia Research Institute at UCL, London WC1E 6BT, UK; Corresponding authorNetherlands Institute for Neuroscience, 1105 BA Amsterdam, the Netherlands; Corresponding authorSummary: microRNA-132 (miR-132), a known neuronal regulator, is one of the most robustly downregulated microRNAs (miRNAs) in the brain of Alzheimer’s disease (AD) patients. Increasing miR-132 in AD mouse brain ameliorates amyloid and Tau pathologies, and also restores adult hippocampal neurogenesis and memory deficits. However, the functional pleiotropy of miRNAs requires in-depth analysis of the effects of miR-132 supplementation before it can be moved forward for AD therapy. We employ here miR-132 loss- and gain-of-function approaches using single-cell transcriptomics, proteomics, and in silico AGO-CLIP datasets to identify molecular pathways targeted by miR-132 in mouse hippocampus. We find that miR-132 modulation significantly affects the transition of microglia from a disease-associated to a homeostatic cell state. We confirm the regulatory role of miR-132 in shifting microglial cell states using human microglial cultures derived from induced pluripotent stem cells.http://www.sciencedirect.com/science/article/pii/S2589004223009069Molecular biologyNeuroscienceOmics |
| spellingShingle | Hannah Walgrave Amber Penning Giorgia Tosoni Sarah Snoeck Kristofer Davie Emma Davis Leen Wolfs Annerieke Sierksma Mayte Mars Taofeng Bu Nicola Thrupp Lujia Zhou Diederik Moechars Renzo Mancuso Mark Fiers Andrew J.M. Howden Bart De Strooper Evgenia Salta microRNA-132 regulates gene expression programs involved in microglial homeostasis iScience Molecular biology Neuroscience Omics |
| title | microRNA-132 regulates gene expression programs involved in microglial homeostasis |
| title_full | microRNA-132 regulates gene expression programs involved in microglial homeostasis |
| title_fullStr | microRNA-132 regulates gene expression programs involved in microglial homeostasis |
| title_full_unstemmed | microRNA-132 regulates gene expression programs involved in microglial homeostasis |
| title_short | microRNA-132 regulates gene expression programs involved in microglial homeostasis |
| title_sort | microrna 132 regulates gene expression programs involved in microglial homeostasis |
| topic | Molecular biology Neuroscience Omics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223009069 |
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