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Series GSE148882 Query DataSets for GSE148882
Status Public on Jun 01, 2020
Title Multi-omics analysis of hematopoietic progenitors in the fetal liver of Mettl3 deficient mice
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary N6-methyladenosine (m6A) is the most abundant RNA modification, but little is known about its role in mammalian hematopoietic development. Conditional deletion of the m6A writer METTL3 in murine fetal liver results in hematopoietic failure and perinatal lethality. Loss of METTL3 and m6A activates an aberrant innate immune response, mediated by the formation of endogenous double-stranded RNAs (dsRNAs). The aberrantly formed dsRNAs are long, highly m6A modified in their native state, characterized by low folding energies and predominantly protein-coding. We identified coinciding activation of innate immune pattern recognition receptor pathways normally tasked with the detection of foreign dsRNAs. Our results suggest that m6A modification protects against endogenous dsRNA formation and a deleterious innate immune response during mammalian hematopoietic development.
Keywords: innate immune response, dsRNA, RNA modification, N6-methyladenosine, METTL3, hematopoietic development, RNA-seq, H3K4me3, CUT&RUN, J2-RIP, dropseq, single cell RNA-seq, scRNA-seq, LSK, fetal liver
 
Overall design In this study, we performed multi-omics high-throughput sequencing of hematopoietic progenitors from the fetal liver of Mettl3 deficient and control mice, to determine the function of Mettl3 mediated m6A in the context of hematopoiesis. Bulk RNA-seq was performed in biological triplicate. H3K4me3 CUT&RUN was performed in biological duplicate. J2-RIP and INPUT controls were performed in biological duplicate. Single cell RNA-seq was performed in biological duplicate.

The files below contain raw counts:
Mettl3_bulk_RNAseq_counts.txt: tab-delimited text file including gene annotations (columns 1-4) and sample-specific counts of aligned reads (bulk RNA-seq, Mettl3 depleted and wild type).
Mettl3_H3K4me3_TSS_3k_counts.txt: tab-delimited text file including transcript annotations (columns 1-6) and sample specific counts of H3K4me3 CUT&RUN reads aligned in the TSS region, considering a window of 3kb (Mettl3 depleted and wild type).
Mettl3_J2_RNAseq_counts.txt: tab-delimited text file including gene annotations (columns 1-4) and sample-specific counts of aligned reads (for both J2-RIP and INPUT samples, Mettl3 depleted and wild type).
Mettl3_singlecell_RNAseq_counts.txt: tab-delimited text file containing gene-specific and cell-specific counts (single cell RNA-seq, Mettl3 depleted and wild type).
 
Contributor(s) Gao Y, Vasic R, Nelakanti R, Dura B, Fan R, Xiao A, Tebaldi T, Halene S
Citation(s) 32497523
Submission date Apr 18, 2020
Last update date Nov 13, 2020
Contact name Toma Tebaldi
E-mail(s) toma.tebaldi@yale.edu, toma.tebaldi@unitn.it
Organization name Yale University & University of Trento
Department CIBIO & Department of Internal Medicine, Yale Cancer Center
Lab Laboratory of RNA and Disease Data Science (RDDS)
Street address 300 George Street
City New Haven, US & Trento, Italy
State/province CT
ZIP/Postal code 06511
Country USA
 
Platforms (2)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (22)
GSM4485104 Mettl3 KO fetal liver LSK bulk RNA-seq rep 1
GSM4485105 Mettl3 KO fetal liver LSK bulk RNA-seq rep 2
GSM4485106 Mettl3 KO fetal liver LSK bulk RNA-seq rep 3
Relations
BioProject PRJNA626093
SRA SRP257219

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE148882_Mettl3_H3K4me3_TSS_3k_counts.txt.gz 2.0 Mb (ftp)(http) TXT
GSE148882_Mettl3_J2_RNAseq_counts.txt.gz 625.6 Kb (ftp)(http) TXT
GSE148882_Mettl3_bulk_RNAseq_counts.txt.gz 634.2 Kb (ftp)(http) TXT
GSE148882_Mettl3_singlecell_RNAseq_counts.txt.gz 18.5 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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