microRNA-132 regulates gene expression programs involved in microglial homeostasis

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

doi:10.1016/j.isci.2023.106829

microRNA-132 regulates gene expression programs involved in microglial homeostasis

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

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Abstract

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.

Original language	English
Pages (from-to)	106829
Journal	iScience
Volume	26
Issue number	6
DOIs	https://doi.org/10.1016/j.isci.2023.106829
Publication status	Published - 01 Jun 2023

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10.1016/j.isci.2023.106829

Walgrave2023Final published version, 5.13 MBLicence: CC BY

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Walgrave, H., Penning, A., Tosoni, G., Snoeck, S., Davie, K., Davis, E., Wolfs, L., Sierksma, A., Mars, M., Bu, T., Thrupp, N., Zhou, L., Moechars, D., Mancuso, R., Fiers, M., Howden, A. J. M., De Strooper, B., & Salta, E. (2023). microRNA-132 regulates gene expression programs involved in microglial homeostasis. iScience, 26(6), 106829. https://doi.org/10.1016/j.isci.2023.106829

@article{5400d872fa1a49a0b358d7c9697317d1,

title = "microRNA-132 regulates gene expression programs involved in microglial homeostasis",

abstract = "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.",

author = "Hannah Walgrave and Amber Penning and Giorgia Tosoni and Sarah Snoeck and Kristofer Davie and Emma Davis and Leen Wolfs and Annerieke Sierksma and Mayte Mars and Taofeng Bu and Nicola Thrupp and Lujia Zhou and Diederik Moechars and Renzo Mancuso and Mark Fiers and Howden, {Andrew J M} and {De Strooper}, Bart and Evgenia Salta",

note = "{\textcopyright} 2023 The Author(s).",

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doi = "10.1016/j.isci.2023.106829",

language = "English",

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Walgrave, H, Penning, A, Tosoni, G, Snoeck, S, Davie, K, Davis, E, Wolfs, L, Sierksma, A, Mars, M, Bu, T, Thrupp, N, Zhou, L, Moechars, D, Mancuso, R, Fiers, M, Howden, AJM, De Strooper, B & Salta, E 2023, 'microRNA-132 regulates gene expression programs involved in microglial homeostasis', iScience, vol. 26, no. 6, pp. 106829. https://doi.org/10.1016/j.isci.2023.106829

TY - JOUR

T1 - microRNA-132 regulates gene expression programs involved in microglial homeostasis

AU - Walgrave, Hannah

AU - Penning, Amber

AU - Tosoni, Giorgia

AU - Snoeck, Sarah

AU - Davie, Kristofer

AU - Davis, Emma

AU - Wolfs, Leen

AU - Sierksma, Annerieke

AU - Mars, Mayte

AU - Bu, Taofeng

AU - Thrupp, Nicola

AU - Zhou, Lujia

AU - Moechars, Diederik

AU - Mancuso, Renzo

AU - Fiers, Mark

AU - Howden, Andrew J M

AU - De Strooper, Bart

AU - Salta, Evgenia

PY - 2023/6/1

Y1 - 2023/6/1

N2 - 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.

AB - 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.

U2 - 10.1016/j.isci.2023.106829

DO - 10.1016/j.isci.2023.106829

M3 - Article

C2 - 37250784

SN - 2589-0042

VL - 26

SP - 106829

JO - iScience

JF - iScience

IS - 6

ER -

microRNA-132 regulates gene expression programs involved in microglial homeostasis

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