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Table 3 Summary of publications and preprints using the six basic protocols for the generation of microglia-like cells from human pluripotent stem cells for basic microglia research or translational applications

From: Generating microglia from human pluripotent stem cells: novel in vitro models for the study of neurodegeneration

First author / YearMGL protocolmutant hPSCsmain findings
Muffat et al. 2016 [21]Muffat-MGLMECP2−/−smaller microglia diameter.
Gosselin et al. 2017 [33]Muffat-MGLn/aThe transcriptome of MGLs closely resembles primary microglia cultured in vitro but differ significantly from microglia ex vivo.
Muffat et al. 2018 [34]Muffat-MGLn/aInfected primitive yolk sac macrophages may act as ZIKV reservoir during pregnancy and establish brain infection upon colonising the developing CNS.
Lin et al. 2018 [35]Muffat-MGLAPOE (ε3 vs. ε4)APOE4 perturbs several microglial functions preventing microglia from clearing Aβ from AD brain organoids effectively.
Brownjohn et al. 2018 [36]Haenseler-MGLTREM2T66M; −W50Closs of TREM2 surface expression; reduced mature isoforms; reduced TREM2 proteolysis.
Garcia-Reitboeck et al. 2018 [37]Haenseler-MGLTREM2T66M; −W50Creduced or absent soluble TREM2 in supernatants.
Xiang et al. 2018 [13]Haenseler-MGL (modified)TREM2R47Hnormal TREM2 mRNA and protein expression and splicing patterns.
Piers et al. 2019 [38]Haenseler-MGL (Xiang)TREM2T66M; −W50C; −R47Hmetabolic deficits: a reduced mitochondrial respiratory capacity and an inability to perform a glycolytic immunometabolic switch, due to dysregulated PPARγ/p38MAPK signalling.
Hasselmann et al. 2019 [39]Abud-MGL (McQuade)TREM2R47HHPSC-derived hematopoietic progenitors engraft in the postnatal mouse brain and adopt the transcriptional identity of human primary microglia. TREM2 mutant microglia displayed reduced migration towards Aβ plaques.
Claes et al. 2019 [40]Douvaras-MGL (modified)TREM2R47H; +/−; −/−Isogenic hetero- and homozygous TREM2 knockouts resulted in reduced phagocytosis of E. coli fragments in vitro and amyloid plaques in AD mouse brain slices. TREM2R47H mutant MGLs displayed normal phagocytosis.
Mancuso et al. 2019 [41]Douvaras-MGL (modified)n/aHESC-derived monocytes engraft in the postnatal mouse brain and adopt the transcriptional identity of human primary microglia.
Takata et al. 2017 [30]Takata-MGLMEFVM694Vincreased secretion of pro-inflammatory cytokines; increased ASC-speck formation.