| Experiment Id | GSE148882 | Name | Multi-omics analysis of hematopoietic progenitors in the fetal liver of Mettl3 deficient mice |
| Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2024-11-06 |
| description | 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 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). |
