KEY RESOURCES TABLE

REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
METTL3/MT-A70 Antibody	Bethyl lab	Cat# A301-567A; RRID: AB_1040004
Anti-METTL14 antibody	SIGMA-ALDRICH	Cat# HPA038002; RRID: AB_10672401
Anti-m6A antibody	Synaptic Systems	Cat# 202003; RRID: AB_2279214
Anti-PKR antibody	SIGMA-ALDRICH	Cat# SAB3500326; RRID: AB_10646199
Anti-phospho-PKR antibody	SIGMA-ALDRICH	Cat# SAB4504517;
eIF2α Antibody	Cell Signaling Technology	Cat# 9722S; RRID: AB_2230924
Phospho-eIF2α (Ser51) Antibody	Cell Signaling Technology	Cat# 9721S; RRID: AB_330951
CD34 Monoclonal Antibody (RAM34), FITC	eBioscience	Cat# 11-0341-85; RRID: AB_465021
PE/Cy5 anti-mouse CD135 (Flt3) Antibody	Biolegend	Cat# 135312; RRID: AB_2263031
Miltenyi lineage detection	Miltenyi	Cat# 130-092-613; RRID: AB_1103214
APC-Cy7 Streptavidin	Biolegend	Cat# 405208
PE anti-mouse Ly-6A/E (Sca-1) Antibody	Biolegend	Cat# 108108; RRID: AB_313345
APC anti-mouse CD117 (c-Kit) Antibody	Biolegend	Cat# 105812; RRID: AB_313221
Purified Rat Anti-Mouse CD16/CD32 (Mouse BD Fc Block™)	BD Biosciences	Cat# 553142; RRID: AB_394657
CD16/CD32 Monoclonal Antibody, PE-Cy7	eBioscience	Cat# 25-0161-82; RRID: AB_469597
APC anti-mouse/human CD44 Antibody	Biolegend	Cat# 103012; RRID: AB_312963
TER-119 Monoclonal Antibody (TER-119), PE	Biolegend	Cat# 12-5921-82; RRID: AB_466042
Biotin anti-mouse Ly-6G/Ly-6C (Gr-1) Antibody	Biolegend	Cat# 108404; RRID: AB_313369
Biotin anti-mouse/human CD45R/B220 Antibody	Biolegend	Cat# 103204; RRID: AB_312989
CD11b Monoclonal Antibody (M1/70), Biotin	eBioscience	Cat# 13-0112-82; RRID: AB_466359
Streptavidin eFluor™ 450	eBioscience	Cat# 48-4317-82; RRID: AB_10359737
Pacific Blue™ anti-mouse/human CD11b	Biolegend	Cat# 101224; RRID: AB_755986
APC anti-mouse Ly-6G/Ly-6C (Gr-1) Antibody	Biolegend	Cat# 108411; RRID: AB_313376
PE/Cy7 anti-mouse CD45.1 Antibody	Biolegend	Car# 110730; RRID: AB_1134168
CD45.2 Monoclonal Antibody (104), FITC	eBioscience	Cat# 11-0454-85; RRID: AB_465060
HSP90 Antibody	StressMarq Biosciences	Cat# SMC-107; RRID: AB_854214
GAPDH (FL-335) Antibogy	Santa Cruz Biotechnology	Cat# sc-25778; RRID: AB_10167668
Anti-rabbit IgG, HRP-linked Antibody	Cell Signaling Technology	Cat# 7074; RRID: AB_2099233
goat anti-mouse IgG-HRP	Santa Cruz Biotechnology	Cat# sc-2031; RRID: AB_631737
Histone H3K4me3 antibody (pAb)	Active motif	Cat# 39159; RRID: AB_2615077
Normal Rabbit IgG	Millipore	Cat# 12-370; RRID: AB_145841
Monoclonal Antibody SCICONS J2	English & Scientific Consulting Kft.	Cat# 10010200; RRID: AB_2651015
Cy3 Streptavidin	VECTOR LABORATORIES	Cat# SA-1300
Cy5 Streptavidin	VECTOR LABORATORIES	Cat# SA-1500
Chemicals, Peptides, and Recombinant Proteins
MethoCult™ GF M3434	STEMCELL Technologies	Cat# 03434
Phusion High-Fidelity PCR Master Mix with HF Buffer	New England Biolabs	Cat# M0531L
RBC Lysis Buffer, 10X	Santa Cruze Biotechnology	Cat# sc-296258
Lipofectamine™ 2000 Transfection Reagent	ThermoFisher SCIENTIFIC	Cat# 11668019
Lipofectamine™ RNAiMAX Transfection Reagent	ThermoFisher SCIENTIFIC	Cat# 13778100
Mouse Thrombopoietin (mTPO)	Gemini Bio-product	Cat# 300-351P
Mouse Stem Cell Factor (mSCF)	Gemini Bio-product	Cat# 300-348P
Mouse Flt-3 Ligand (mFlt3L)	Gemini Bio-product	Cat# 300-306P
Mouse Interleukin-3 (mIL3)	Gemini Bio-product	Cat# 300-324P
Benchmark Fetal Bovine Serum (FBS)	Gemini Bio-product	Cat# 100-106
DMEM, high glucose	ThermoFisher SCIENTIFIC	Cat# 11965092
Protein A–micrococcal nuclease (pA-MN) fusion protein	Henikoff lab	Skene and Henikoff, 2018
Spermidine trihydrochloride	Sigma-Aldrich	Cat# S2501
Con A-coated BioMag®Plus microparticles	Polysciences, Inc	Cat# 86057-3
iQ™ SYBR® Green Supermix	BIO-RAD	Cat# 1708880
iScript cDNA Synthesis Kit	BIO-RAD	Cat# 1708890
cOmplete™, Mini, EDTA-free Protease Inhibitor Cocktail	Sigma-Aldrich	Cat# 11836170001
SUPERase• In™ RNase Inhibitor	ThermoFisher SCIENTIFIC	Cat# AM2696
SPRIselect beads	Beckman Coulter	Cat# B23317
RNaseA, Dnase and protease-free	ThermoFisher SCIENTIFIC	Cat# EN0531
Maxima H Minus Reverse Transcriptase	ThermoFisher SCIENTIFIC	Cat# EP0752
Exonuclease I	New England Biolabs	Cat# M0293S
Ampure XP beads	Beckman Coulter	Cat# A63880
Fluorinert™ FC-40	Sigma-Aldrich	Cat# F9755
Critical Commercial Assays
EpiQuik m6A RNA Methylation Quantification Kit (Colorimetric)	Epigentek	Cat# P-9005-96
FITC BrdU Flow Kits	BD Pharmingen™	Cat# 559619
CellTrace CFSE Cell Proliferation Kit, for flow	Thermo Fisher	Cat# C34554
FITC Annexin V Apoptosis Detection Kit I	BD Pharmingen™	Cat# 556547
RNeasy Mini Kit	QIAGEN	Cat# 74106
RNeasy Plus Micro Kit	QIAGEN	Cat# 74034
Magnetic mRNA Isolation Kit	New England Biolabs	Cat# S1550S
MinElute PCR Purification Kit	QIAGEN	Cat# 28004
NEBNext Multiplex Oligos for Illumina	New England Biolabs	Cat# E7500S
NEBNext Ultra II DNA Library Prep Kit	New England Biolabs	Cat# E7645S
Qubit dsDNA HS Assay Kit	Life Technologies	Cat# Q32851
Vector M.O.M. Immunodetection Kit	VECTOR LABORATORIES	Cat# BMK-2202
Deposited Data
Raw and analyzed data	This paper	GEO: GSE148882
Mouse genome and transcript annotation	Gencode M15	https://www.gencodegenes.org/mouse/release_M15.html
Transcript sequences	Ensembl 90	https://useast.ensembl.org/info/website/archives/index.html
Annotation of Transposable Elements	Hammell Lab	http://labshare.cshl.edu/shares/mhammelllab/www-data/TEtranscripts/TE_GTF/mm10_rmsk_TE.gtf.gz
Annotation of m6A genes	Barbieri et al., 2017	DOI: 10.1038/nature24678
Annotation of m6A genes	Geula et al., 2015	DOI: 10.1126/science.1261417
Annotation of m6A genes	Li et al., 2018	DOI: 10.1038/s41422-018-0072-0
Annotation of m6A genes	Liu et al., 2020	DOI: 10.1016/j.molcel.2019.09.032
Annotation of m6A genes	Vu et al., 2017	DOI: 10.1038/nm.4416
Experimental Models: Cell Lines
Human: HEK293GP cells	Clontech	Cat# 631458
Human: HEK293T cells	ATCC	Cat# CRL-3216
Experimental Models: Organisms/Strains
Mouse: B6.SJL-Ptprca Pepcb/BoyJ	In house colony	JAX: 002014
Mouse: B6.Cg-Commd10Tg(Vav1-icre)A2Kio/J	In house colony	JAX: 008610
Mouse: C57BL/6J	In house colony	JAX: 000664
Mouse: Mettl3f/f	Li et al., 2017	N/A
Oligonucleotides
ON-TARGETplus Mouse Rnasel siRNA smartpool	Horizon Discovery	L-043480-00-0020
ON-TARGETplus Non-targeting Control Pool	Horizon Discovery	D-001810-10-05
See Table S3	This paper	N/A
Recombinant DNA
pMSCV-IRES-GFP	Addgene	Plasmid #20672
pMSCV-Mettl3-GFP	This paper	N/A
pMSCV-Mettl3CD-GFP	This paper	N/A
LentiCRISPRv2-mCherry	Addgene	Plasmid #99154
LentiCRISPRv2- Mavs-mCherry	This paper	N/A
LentiCRISPRv2-Control-mCherry	This paper	N/A
pCMV-VSV-G	Addgene	Plasmid #8454
psPAX2	Addgene	Plasmid #12260
Software and Algorithms
FlowJo v10	FlowJo, LLC	https://www.flowjo.com/solutions/flowjo
Prism v8	GraphPad	https://www.graphpad.com/scientific-software/prism/
Bowtie2 v2.2.9	John Hopkins University	http://bowtie-bio.sourceforge.net/bowtie2/index.shtml
Fiji	NIH	https://fiji.sc/
Drop-seq tools v1.12	Broad Institute	https://github.com/broadinstitute/Drop-seq
STAR v2.3.3a	N/A	https://github.com/alexdobin/STAR
edgeR	Bioconductor	https://bioconductor.org/packages/release/bioc/html/edgeR.html
clusterProfiler	Bioconductor	https://bioconductor.org/packages/release/bioc/html/clusterProfiler.html
Picard Tools v2.9.0	Broad Institute	https://broadinstitute.github.io/picard/
Fastuniq v1.1	N/A	https://sourceforge.net/projects/fastuniq/
RNAfold v2.4.11	ViennaRNA package	https://www.tbi.univie.ac.at/RNA/
Rsubread	Bioconductor	https://bioconductor.org/packages/release/bioc/html/Rsubread.html
Seurat v3.0	N/A	https://satijalab.org/seurat/
FastQC v0.11.5	N/A	https://www.bioinformatics.babraham.ac.uk/projects/fastqc/
Other
Qubit fluorometer	ThermoFisher SCIENTIFIC	Cat# Q33216
HiSeq 2500 Sequencing System	Illumina	Cat# SY–401–2501
HemaTrue Veterinary Hematology Analyzer	Heska	N/A
Leica TCS SP5	Leica	N/A