REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Amyloid Fibrils OC antibody	Millipore	Cat# AB2286 RRID:AB_1977024
mouse Amyloid 1-16aa (6e10)	BioLegend	Cat# 803001 RRID:AB_2564653
mouse β3Tubulin	BioLegend	Cat# 801201 RRID:AB_2313773
mouse SC121 (human cytoplasm)	Takara Bio Inc	Cat# AB-121-U-050, RRID:AB_2632385
mouse ku80 (human nuclei)	Abcam	Cat # ab79220, RRID:AB_1603596
chicken GFAP	Abcam	Cat# ab50738, RRID:AB_880201
rabbit Iba1	Wako	Cat# 27030, RRID:AB_2314667
goat Iba1	Abcam	Cat# ab5076, RRID:AB_2224402
mouse ITGB5	Abcam	Cat# ab177004
mouse MMP9	Millipore	Cat# AB19016, RRID:AB_11211211
mouse MERTK	BioLegend	Cat# 367602, RRID:AB_2565898
rabbit P2RY12	Sigma	Cat# HPA014518
Rabbit PROS1	Abcam	Cat# ab97387, RRID:AB_10695954
rabbit PU1	Cell Signaling Technology	Cat# 2266S, RRID:AB_10692379
rabbit TMEM119 (human, C-terminus)	Abcam	Cat# ab185333
goat TREM2 (human)	R and D Systems	Cat# AF1828, RRID:AB_2208689
rabbit TGFBR1	Abcam	Cat# ab31013, RRID:AB_778352
rabbit CX3CR1	Bio-Rad/AbD Serotec	Cat# AHP1589, RRID:AB_2087421
LEAF Purified anti-human CD11b	BioLegend	Cat# 301312, RRID:AB_314164
Tau (T22), oligomeric	EMD Milipore	Cat# ABN454
APC-Cyanine7 CD45 (HI30)	Tonbo Biosciences	Cat# 25-0459-T10
PE/Cy7 CD235a (Glycophorin A) (clone HI264)	BioLegend	Cat# 349112, RRID:AB_2562708
APC CD43 Antibody (clone CD43-10G7)	BioLegend	Cat# 343206, RRID:AB_2194072
FITC CD34 Antibody (clone 561)	BioLegend	Cat# 343604, RRID:AB_1732005
PE CD41 Antibody (clone HIP8)	BioLegend	Cat# 303706, RRID:AB_314376
Zombie Violet™ Fixable Viability Stain	BioLegend	Cat# 423114
Biological Samples
Human adult microglia RNA	This paper	N/A
Human fetal microglia RNA	This paper	N/A
Human PBMCs	This paper	N/A
Human fetal tissue	This paper	N/A
Chemicals, Peptides, and Recombinant Proteins
Human TGFβ1	Miltenyi	Cat# 130-108-969
Human IL34	Peprotech	Cat# 200-34
Human MCSF	Thermo Fisher Scientific	Cat# PHC9501
Human FGF2	Thermo Fisher Scientific	Cat# PHG0261
Human BMP4	Thermo Fisher Scientific	Cat# PHC9531
Human Activin A	Thermo Fisher Scientific	Cat# PHC9564
Human TPO	Thermo Fisher Scientific	Cat# PHC9514
Human IL6	Thermo Fisher Scientific	Cat# PHC0061
Human IL3	Thermo Fisher Scientific	Cat# PHC0031
Human VEGF	Thermo Fisher Scientific	Cat# PHC9391
Human SCF	Thermo Fisher Scientific	Cat# PHC2111
Human Fractalkine (CX3CL1)	Peprotech	Cat# 300-31
Human CD200	Novoprotein	Cat# C311-50ug
BD Matrigel Matrix Growth Factor Reduced, Phenol Red-Free	BD Biosciences	Cat# 356231
TeSR™-E8™	STEMCELL Technologies	Cat# 05940
IMDM (Iscove’s Modified Dulbecco’s Medium)	Thermo Fisher Scientific	Cat# 12440053
Ham’s F12	Thermo Fisher Scientific	Cat# 11765054
DMEM/F-12, HEPES, no phenol red	Thermo Fisher Scientific	Cat# 11039021
RPMI 1640 Medium, no phenol red	Thermo Fisher Scientific	Cat# 11835030
BSA solution	Miltenyi	Cat# 130-091-376
Lithium Chloride solution	Sigma	Cat# L7026-100ML
L-Ascorbic acid 2-phosphate sesquimagnesium salt hydrate	Sigma	Cat# A8960-5G
1-Thioglycerol (Monothioglycerol)	Sigma	Cat# M1753-100ML
Poly-vinyl-Alcohol (PVA)	Sigma	Cat# P8136-250G
B27 Supplement	Thermo Fisher Scientific	Cat# 17504044
N2 Supplement	Thermo Fisher Scientific	Cat# 17502048
Non-essential Amino Acids (NEAA)	Thermo Fisher Scientific	Cat# 11140050
GlutaMax Supplement	Thermo Fisher Scientific	Cat# 35050061
ROCK inhibitor Y-27632	R and D Systems	Cat# 1254
Human Insulin	Sigma	Cat# I2643-50MG
Insulin-Transferrin-Selenium (ITS-G) (100X)	Thermo Fisher Scientific	Cat# 41400045
Insulin-Transferrin-Selenium-Ethanolamine (ITS -X) (100X)	Thermo Fisher Scientific	Cat# 51500056
Penicillin-Streptomycin	Thermo Fisher Scientific	Cat# 15140122
Adenosine 5′-diphosphate	Sigma	Cat# 01905-250MG-F
PSB 0739	Tocris	Cat# 3983
Fura-2, AM, cell permeant	Thermo Fisher Scientific	Cat# F1201
May-Grünwald Stain	Sigma	Cat# MG1L SIGMA
Giemsa Stain	Sigma	Cat# GS500-500ML
Beta - Amyloid (1 - 42), Human	Anapsec	Cat# AS-20276
Beta - Amyloid (1 - 42), HiLyte™ Fluor 555 - labeled, Human	Anapsec	Cat# AS-60480-01
Human Brain derived Tau Oligomers	This paper	N/A
Human Brain derived Synaptosomes	This paper	N/A
pHrodo Red Dye	Thermo Fisher Scientific	Cat# P36600
RNA-later	Thermo Fisher Scientific	Cat# AM7021
KnockOut Replacement Serum (KOSR)	Thermo Fisher Scientific	Cat# 10828028
Fetal Bovine Serum	Thermo Fisher Scientific	Cat# 10437028
Lipidure-coated 96 well V-bottom plate	AMSbio	Cat# AMS.51011612
Amylo-Glo RTD Amyloid Plaque Stain Reagent	Biosensis	Cat# TR-300-AG
TrypLE™ Select Enzyme (1X), no phenol red	Thermo Fisher Scientific	12563029
Critical Commercial Assays
Human Pluripotent Stem Cell Functional Identification Kit	R and D Systems	Cat# SC027B
V-PLEX Human Cytokine 30-Plex	Meso Scale Discovery	Cat# K15054D-1
nCounter Human Copy Number Variants	Nanostring	Cat# 115000102
nCounter Human Copy Number Variants Master Kit	Nanostring	Cat# 100052
Kapa Library Quantification Kit	Kappa Biosystems	N/A contact ucightf@gmail.com
TruSeq RNA Library Prep Kit v2	Illumina	N/A contact ucightf@gmail.com
Qiagen RNA kit	Qiagen	Cat# 74106
cDNA kit	Thermo Fisher Scientific	Cat# 11754050
EasySepTM Monocyte Enrichment Kit	STEMCELL Technologies	19059
EasySep™ Human Pan-DC Pre-Enrichment Kit	STEMCELL Technologies	19251
Deposited Data
RNA-Seq Data	This Paper	GEO GSE89189
Experimental Models: Cell Lines
Rat Hippocampal neurons	This paper	N/A
Commercial iHPCs (Lot# 021405)	Cellular Dynamics International	Cat# HPC-301-020-001-PT
Human: iPSC line from Fibroblast- Male	UCI ADRC iPSC Core	ADRC 2
Human: iPSC line from Fibroblast-Male	UCI ADRC iPSC Core	ADRC 4
Human: iPSC line from Fibroblast-Female	UCI ADRC iPSC Core	ADRC 5
Human: iPSC line from PBMC-Male	UCI ADRC iPSC Core	ADRC 12
Human: iPSC line from Fibroblast-Male	UCI ADRC iPSC Core	ADRC F14
Human: iPSC line from Fibroblast- Female	UCI ADRC iPSC Core	ADRC 20
Human: iPSC line from PBMC-Female	UCI ADRC iPSC Core	ADRC 22
Human: iPSC line from PBMC-Male	UCI ADRC iPSC Core	ADRC 76
Human: iPSC line from Fibroblast-Male	UCI ADRC iPSC Core	ADRC 85
Human: iPSC line from Fibroblast -Female	UCI ADRC iPSC Core	ADRC 86
Human: fetal-derived microglia- Sex N/A	This paper	N/A
Human: Monocytes – Sex in Method Details	This paper	N/A
Human: Monocyte-derived macrophages	This paper	N/A
Human: Blood borne Dendritic Cells Sex in Method Details	This Paper	N/A
Human: iPSC-derived HPCs	This paper	N/A
Experimental Models: Organisms/Strains
Rag-5xfAD; mouse: B6.Cg-Tg (APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax crossed with mouse: B10;B6-Rag2tm1Fwa Il2rgtm1Wjl From Jackson Laboratory and Taconic, respectively.	Blurton-Jones lab, UC Irvine, CA.	(Marsh, et al. PNAS, 2016)
MITRG; mouse M-CSFh;IL-3/GM-CSFh;THPOh;Rag2−;γc−	The Jackson Laboratory	Jax: 017711
Rat: Sprague Dawley Crl:SD	Charles River	Charles River strain code: 400
Oligonucleotides
Primers for qPCR, see Table S7	Thermo Fisher Scientific	see Table S7
Software and Algorithms
STAR	(Dobin et al., 2013)	https://github.com/alexdobin/STAR
RSEM	(Li and Dewey, 2011)	https://deweylab.github.io/RSEM/
EdgeR	(Robinson et al., 2010)	http://bioconductor.org/packages/edgeR/
Rstudio	N/A	https://www.rstudio.com/
Java Tree View 3.0	N/A	(http://bonsai.hgc.jp/~mdehoon/software/cluster/software.htm)
Enrichr	(Chen et al., 2013; Kuleshov et al., 2016)	http://amp.pharm.mssm.edu/Enrichr/)
FlowJo v10.0	N/A	https://www.flowjo.com/solutions/flowjo
GraphPad Prism v7	N/A	https://www.graphpad.com/scientific-software/prism/
Other
BD FACSARIA Fusion	BD Biosciences	equipment
Amnis ImageStreamX Mark II Image Flow Cytometer	EMD Milipore	equipment