REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Anti-Rabbit Alexa Fluor 488	Thermofisher	Cat# A21206
Anti-Goat Alexa Fluor 488	Thermofisher	Cat# A11055
Anti-Tmem106b	Bethyl	Cat # A303-439A
Anti-Tmem106b	Cell Signaling	Cat # 93334
Anti-Aif1 human	Wako Fujifilm	Cat# 019-19741
Anti-Trem2 human	R&D Systems	Cat #: AF1828
Anti-Cathepsin D (chromogenic staining)	Abcam	Cat# ab75852
Anti-Cathepsin D (IF staining)	R & D	Cat# AF1029
Anti-Lamp1	Abcam	Cat# ab25245
Anti-Iba1	Wako	Cat#019–19741; RRID: AB_839504
Anti-ChaT	Millipore	Cat#AB144P; RRID: AB_2079751
Anti-CD68	Biorad	Cat#MCA1957T; RRID: AB_2074849
Anti-dMBP	Millipore	Cat#AB5864;RRID: AB_2140351
Anti-NeuN	Synaptic Systems	Cat# 266004
Rabbit polyclonal Anti-ASO antibody (0.5 μg/mL)	Genentech, Inc.	W138- 442
Bacterial strains
Phrodo Green Zymosan Particles	Thermofisher	Cat #P35365
Chemicals, peptides, and recombinant proteins
Tandem Mass Tags	ThermoFisher Scientific	Cat # A44522
cOMplete, Mini Protease Inhibitor Cocktail	Sigma-Aldrich	Cat # 11836153001
PhosSTOP, Phosphatase Inhibitor	Sigma-Aldrich	Cat # 4906837001
Dithiothreitol	ThermoFisher Scientific	Cat # A39255
Iodoacetemide	ThermoFisher Scientific	Cat # A39271
Lysyl endopeptidase	FujiFilm Wako Chemicals	Cat # 125-05061
Sequencing Grade Modified Trypsin	Promega	Cat #V5113
hydroxylamine	ThermoFisher Scientific	Cat # 90115
Critical commercial assays
Mouse neurofilament light	Quanterix	Simoa NF-Light Advantage Kit (#103186)
StemDiff hematopoietic kit	Stemcell Technologies	cat #05310
StemDiff microglia differentiation kit	Stemcell Technologies	cat #100-0019; cat #100-0020
Quickstart Bradford Protein Assay Kit	Bio-Rad	Cat # 500202
Deposited data
iMG Proteomics	MassIVE	MSV000090254
Transcriptomics (Mouse and Human microglia)	GEO	GSE237107
Experimental models: Cell lines
PGP1 TMEM106B KO iPS line	Synthego	custom
PGP1 GRN KO iPS line	Synthego	custom
Experimental models: Organisms/strains
Grn −/−	University of Tokyo	NA
TMEM106b −/−	Genentech, Inc.	NA
Oligonucleotides
ETGTATTTCAAATETEA	RICC	ASO 1
ETGTATTTCAAATETEA	RICC	ASO 2
TGACACTATCTCTTEE	RICC	ASO 3
GTATTTCAAATCTEAAAT	RICC	ASO 4
ATTATGTTTATCACEAA	RICC	NC ASO
Critical commercial assays
TMEM106B mouse qPCR probe	Thermofisher Scientific	Cat # 4351370
GAPDH mouse qPCR probe	Applied Biosystems	Cat # 4351309
GRN mouse qPCR probe	Thermofisher	cat# Mm00433848_m1GRN
Software and algorithms
MATLAB for IHC quantification	MathWorks	N/A
JMP		https://www.jmp.com/en_us/home.html
Graphpad Prism v9.0		https://www.graphpad.com/
In-house mass spectrometry data analysis software	Huttlin et al., 201052	N/A
MASCOT	Matrix Science	N/A
R		https://www.r-project.org
MSstats/MSstatsTMT	Huttlin et al., 201052; Huang et al., 202019,53	http://bioconductor.org/packages/release/bioc/html/MSstatsTMT.html
GSNAP	Wu et al., 201654	https://bioconductor.org/packages/release/bioc/html/gmapR.html
HTSeqGenie	Pau & Reeder, 202155	https://bioconductor.org/packages/release/bioc/html/HTSeqGenie.html
Limma	Law et al., 201456	https://bioconductor.org/packages/release/bioc/html/limma.html
ComBat-seq	Zhang et al., 202057	https://bioconductor.org/packages/release/bioc/html/sva.html
Other
SOLA HRP SPE cartridges	ThermoFisher Scientific	Cat # 60109-001
Sep-pak C18 cartridges	Waters	Cat # WAT054925
Aurora Ultimate column	IonOpticks	Cat # 25075C18
Orbitrap Eclipse Mass Spectrometer	ThermoFisher Scientific	Cat # FSN04-10000
Dionex Ultimate 3000 RSLC nano Proflow	ThermoFisher Scientific	Cat # ULTIM3000RSLCNANO