Table 3.

Selected Studies Investigating Neurological Diseases Using iPSC-derived Microglia

Disease	Disease Features of Interest	Disease iPSC Characteristics	Cellular Model	Major Findings
Alzheimer disease (AD)	Effects of sAD risk factor APOE4 on multiple neural cell types [107] Effects of AD-predisposing genetic backgrounds including APOE4, PSEN1ΔE9, and APPswe on the functionality of iMGs[138] Effects of a surrogate brain environment on human microglia [143]	Two-way isogenic APOE3 and APOE4 iPSCs generated by CRISPR APOE4, PSEN1ΔE9, and APPswe iPSCs; PSEN1ΔE9, and APPswe were corrected Isogenic iPSCs by CRISPR control iPSCs and isogenic TREM2 R47H mutant generated by CRISPR	Microglia in vitro Microglia in vitro Microglia ex vivo (xMG; transplantation of iPSC-derived hematopoietic progenitors into the postnatal brain of humanized, immune-deficient mice)	Morphological changes of APOE4 microglia with reduced Aβ phagocytosis Impaired phagocytosis, migration and metabolic activity and increased cytokine secretion in APOE4 microglia; PSEN1ΔE9 and APPswe had minor effects xMGs in contact with Aβ plaques adopted an activated, ameboid morphology
Nasu-Hakola disease (NHD)	Role of TREM2 mutation in NHD [144]	iPSCs from NHD patients with TREM2 T66M and W50C mutations	Microglia in vitro	Impairment in the phagocytosis of apoptotic bodies, but not in Escherichia coli or zymosan substrate in mutant microglia
ZIKA virus (ZIKV) infection	Effect of ZIKV on different neural cell types [140] Effects of microglia antiviral immune response on NPCs [139]	iPSCs from one individual iPSCs from healthy individuals	Microglia infected with MR766 strain of ZIKV and integrated into brain organoids Microglia infected with Brazil strain of ZIKV co-cultured with NPCs	Microglia acted as the reservoir for ZIKV that invaded the neural tissue and initiated the infection Microglia infected by ZIKV transmitted the virus to NPCs and increased NPC apoptosis
Schizophrenia (SCZ)	Synapse density reduction in SCZ brains [145]	iPSCs from SCZ patients	Mic roglia in vitro	Increased synapse elimination by SCZ microglia