GEO series

Mettl3 maintains genome stability of erythroid cells via Mthfd1-mediated nucleotide biosynthesis

GSE298935 Mus musculus (mouse) DNA methylation 16 samples Submitted 2025/06/09 Platform GPL24247Platform GPL21273

At a glance

DNA methylation · mouse · 16 samples

What it is: DNA methylationChemical marks on DNA that help switch genes on or off.
Organism: Mus musculus (mouse)
Samples: 16 samples: 6 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: Methyltransferase complex subunit METTL3 maintains genome stability of erythroid cells via MTHFD1-mediated nucleotide biosynthesisThe Journal of clinical investigation · 2026

Summary (written by the submitters)

N6-methyladenosine (m6A) is a prevalent modification of mammalian mRNA. Increasing evidence has documented diverse roles of m6A in normal cell physiology and diseases. However, our knowledge on the role of the m6A in erythropoiesis is very limited. A previous study implicated the role of METTL3, the catalytic enzyme for m6A modification, in human erythropoiesis in vitro.

Read the full summary ↓

But the function role of METTL3 in vivo has yet to investigated. In this study, we found that deletion of Mettl3 using EpoR-Cre mouse led to microcytic/hypochromic anemia due to defective erythropoiesis along with impaired hemoglobin biosynthesis. Mechanically, Mettl3 deficiency disrupted nucleotide biosynthesis which induced DNA damage, leading to apoptosis of CFU-E cells and cell cycle arrest of erythroblasts. Integrated m6A sequencing and RNA-seq analysis along with biochemical studies identified Mthdf1, a key enzyme involved in nucleotide biosynthesis, as a Mettl3 direct target gene. Furthermore, deletion of Mettl3 led to decreased expression of Mthdf1 accompanied by a shortage of nucleotides dTMP and IMP in erythroid cells. Additionally, inhibition of METTL3 in human erythroid cells led to similar phenotypic and molecular changes, indicating conserved role of METTL3 in human and murine erythropoiesis. Our findings have identified a novel Mettl3-m6A-Mthfd1 axis that plays a critical role in erythropoiesis by maintaining genome stability of erythroid cells via regulation of nucleotide biosynthesis. These findings provide novel insights into the regulatory mechanisms of erythropoiesis.

Published in

Methyltransferase complex subunit METTL3 maintains genome stability of erythroid cells via MTHFD1-mediated nucleotide biosynthesis

Zhang L, Zhao H, Wang S et al. · The Journal of clinical investigation 2026 · PMID 41805631 · doi:10.1172/JCI196578

This dataset

Open GSE298935 in finder → Find more mouse RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE298935_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Look for beta-value tables or raw IDAT files among the supplementary files.

Also filed as BioProject PRJNA1271960 and SRA study SRP589810. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41805631) ↗

Study design

6 conditions, mostly in triplicate

CFUE_Control ×3 CFUE_Kit_low_Mettl3_KO ×3 ProE_Control ×3 ProE_Mettl3_KO ×3 CFUE_Control_IP ×2 CFUE_Control_input ×2

Supports a between-group comparison across 16 samples.

How we read this: 6 replicated groups read from 16 sample titles; they account for 16 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM9026226 CFUE_Control_rep1 CFUE_Control
GSM9026227 CFUE_Control_rep2 CFUE_Control
GSM9026228 CFUE_Control_rep3 CFUE_Control
GSM9026229 CFUE_Kit_low_Mettl3_KO_rep1 CFUE_Kit_low_Mettl3_KO
GSM9026230 CFUE_Kit_low_Mettl3_KO_rep2 CFUE_Kit_low_Mettl3_KO
GSM9026231 CFUE_Kit_low_Mettl3_KO_rep3 CFUE_Kit_low_Mettl3_KO
GSM9026232 ProE_Control_rep1 ProE_Control
GSM9026233 ProE_Control_rep2 ProE_Control
GSM9026234 ProE_Control_rep3 ProE_Control
GSM9026235 ProE_Mettl3_KO_rep1 ProE_Mettl3_KO
GSM9026236 ProE_Mettl3_KO_rep2 ProE_Mettl3_KO
GSM9026237 ProE_Mettl3_KO_rep3 ProE_Mettl3_KO
GSM9026238 CFUE_Control_IP_rep1 CFUE_Control_IP
GSM9026239 CFUE_Control_IP_rep2 CFUE_Control_IP
GSM9026240 CFUE_Control_input_rep1 CFUE_Control_input
GSM9026241 CFUE_Control_input_rep2 CFUE_Control_input

Datasets on a similar topic

GSE99773 Transcriptome analysis of gene expression and single-nucleotide-resolution m6A sites in normal and mettl3 cKO testis samples 10 samples shares mettl3, nucleotide
GSE99771 Transcriptome analysis of gene expression and single-nucleotide-resolution m6A sites in normal and mettl3 cKO testis samples (RNA-Seq) 8 samples shares mettl3, nucleotide
GSE263141 Chloride Nucleotide-Sensitive Channel 1A (CLNS1A) Regulates Genome Stability and Cell Cycle Progression to Control Pathogenic T Helper 17 Cell Function and Autoimmunity [RNA-seq] 18 samples shares nucleotide, stability
GSE296502 A cell-intrinsic glucocorticoid biosynthesis and sensing circuit maintains homeostatic Th17 cell state 46 samples shares biosynthesis, maintains
GSE296482 A cell-intrinsic glucocorticoid biosynthesis and sensing circuit maintains homeostatic Th17 cell state [RNA-seq] 31 samples shares biosynthesis, maintains
GSE239772 Persistent injury-induced mtDNA mutations compromise organ fitness by suppressing nucleotide biosynthesis 24 samples shares biosynthesis, nucleotide
GSE320348 A cell-intrinsic glucocorticoid biosynthesis and sensing circuit maintains homeostatic Th17 cell state [ATAC-seq] 12 samples shares biosynthesis, maintains
GSE267227 Epithelial NSD2 maintains FMOs-mediated taurine biosynthesis to prevent intestinal barrier disruption [RNA-Seq] 6 samples shares biosynthesis, maintains

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.