2021
DOI: 10.3390/cells10112866
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Differential Stimulation of Pluripotent Stem Cell-Derived Human Microglia Leads to Exosomal Proteomic Changes Affecting Neurons

Abstract: Microglial exosomes are an emerging communication pathway, implicated in fulfilling homeostatic microglial functions and transmitting neurodegenerative signals. Gene variants of triggering receptor expressed on myeloid cells-2 (TREM2) are associated with an increased risk of developing dementia. We investigated the influence of the TREM2 Alzheimer’s disease risk variant, R47Hhet, on the microglial exosomal proteome consisting of 3019 proteins secreted from human iPS-derived microglia (iPS-Mg). Exosomal protein… Show more

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Cited by 9 publications
(14 citation statements)
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References 65 publications
(108 reference statements)
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“…Using our previously described protocol, iPS-microglia (iPS-Mg) were generated 19,20,21,22 (Garcia-Reitboeck et al 2018; Xiang et al 2018; Piers et al 2020, Cosker et al 2021). All iPSCs were cultured and passaged routinely in Essential 8 medium (Gibco), iPS-myeloid progenitor cells (iPS-MPro) were harvested from the flask of embryoid bodies and further differentiated with IL-34, MCSF and TGF-β1 for 14 days, plus a final maturation with CX3CL1 and CD200 (all growth factors were from Peprotech, London UK) for 3 more days as previously described 19, 23 (Piers et al 2020; Mallach et al 2021).…”
Section: Methodsmentioning
confidence: 99%
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“…Using our previously described protocol, iPS-microglia (iPS-Mg) were generated 19,20,21,22 (Garcia-Reitboeck et al 2018; Xiang et al 2018; Piers et al 2020, Cosker et al 2021). All iPSCs were cultured and passaged routinely in Essential 8 medium (Gibco), iPS-myeloid progenitor cells (iPS-MPro) were harvested from the flask of embryoid bodies and further differentiated with IL-34, MCSF and TGF-β1 for 14 days, plus a final maturation with CX3CL1 and CD200 (all growth factors were from Peprotech, London UK) for 3 more days as previously described 19, 23 (Piers et al 2020; Mallach et al 2021).…”
Section: Methodsmentioning
confidence: 99%
“…All modules demonstrated strong evidence for high quality Supplementary figure 3 A. Quantification of PI staining to determine the % of dead cells in NT, Dex, RU/Dex pretreated iPS-Mg. Using our previously described protocol, iPS-microglia (iPS-Mg) were generated 19,20,21,22 and passaged routinely in Essential 8 medium (Gibco), iPS-myeloid progenitor cells (iPS-MPro) were harvested from the flask of embryoid bodies and further differentiated with IL-34, MCSF and TGF-β1 for 14 days, plus a final maturation with CX3CL1 and CD200 (all growth factors were from Peprotech, London UK) for 3 more days as previously described 19,23 (Piers et al 2020;Mallach et al 2021).…”
Section: Supplementary Figure 1 Imentioning
confidence: 99%
“…Other human cell lines (i.e., C20) display an altered response to LPS ( Garcia-Mesa et al, 2017 ; Pozzo et al, 2019 ), while establishing primary microglia from post-mortem/cryo-preserved human brain tissue is still challenging. This limitation may be overcome by the analysis of EVs produced by microglia-like cells, differentiated from induced pluripotent stem cells (iPSC), as recently described ( Mallach et al, 2021a , b ; You et al, 2022 ). Several new protocols to generate human microglia in vitro from iPSCs have been reported, which try to mimic the cues that naturally drive microglia differentiation in vivo .…”
Section: How To Obtain and Study Microglial Extracellular Vesiclesmentioning
confidence: 99%
“…Analysis of the molecular composition of microglial EVs in different conditions may help understanding their specific functions. Proteomic analysis of microglial EVs has been performed on different samples: EVs from N9 ( Potolicchio et al, 2005 ) and BV2 ( Yang et al, 2018 ) cell lines, primary rat microglia ( Hooper et al, 2012 ; Drago et al, 2017 ; Mukherjee et al, 2020 ), MACS sorted rat microglia ( Murgoci et al, 2020 ), primary leech microglia ( Arab et al, 2019 ; Lemaire et al, 2019 ), microglia-like cells from human iPSCs ( Mallach et al, 2021a , b ; You et al, 2022 ), CD11b + EVs from human brain tissue ( Cohn et al, 2021 ). Their lipid ( Osteikoetxea et al, 2015 ; Cohn et al, 2021 ; Kumar et al, 2021 ) and small non-coding RNA (miRNA) composition ( Cunha et al, 2016 ; Prada et al, 2018 ; Lemaire et al, 2019 ; Tian et al, 2019 ; Cohn et al, 2021 ; Li et al, 2022 ) have also been investigated.…”
Section: Composition Of Microglial Extracellular Vesiclesmentioning
confidence: 99%
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