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
| First author / Year | MGL protocol | mutant hPSCs | main findings |
|---|---|---|---|
| Muffat et al. 2016 [21] | Muffat-MGL | MECP2−/− | smaller microglia diameter. |
| Gosselin et al. 2017 [33] | Muffat-MGL | n/a | The transcriptome of MGLs closely resembles primary microglia cultured in vitro but differ significantly from microglia ex vivo. |
| Muffat et al. 2018 [34] | Muffat-MGL | n/a | Infected 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-MGL | APOE (ε3 vs. ε4) | APOE4 perturbs several microglial functions preventing microglia from clearing Aβ from AD brain organoids effectively. |
| Brownjohn et al. 2018 [36] | Haenseler-MGL | TREM2T66M; −W50C | loss of TREM2 surface expression; reduced mature isoforms; reduced TREM2 proteolysis. |
| Garcia-Reitboeck et al. 2018 [37] | Haenseler-MGL | TREM2T66M; −W50C | reduced or absent soluble TREM2 in supernatants. |
| Xiang et al. 2018 [13] | Haenseler-MGL (modified) | TREM2R47H | normal TREM2 mRNA and protein expression and splicing patterns. |
| Piers et al. 2019 [38] | Haenseler-MGL (Xiang) | TREM2T66M; −W50C; −R47H | metabolic 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) | TREM2R47H | HPSC-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/a | HESC-derived monocytes engraft in the postnatal mouse brain and adopt the transcriptional identity of human primary microglia. |
| Takata et al. 2017 [30] | Takata-MGL | MEFVM694V | increased secretion of pro-inflammatory cytokines; increased ASC-speck formation. |