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Differentially expressed genes in hematopoietic stem cells after loss of Mettl3

ABSTRACT: Differentially expressed genes in hematopoietic stem cells after loss of Mettl3

PROVIDER: PRJNA509126 | ENA |

REPOSITORIES: ENA

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Differentially expressed genes in hematopoietic stem cells after loss of Mettl3

Project description:Hematopoietic stem cells (HSCs) maintain balanced self-renewal and differentiation according to physiological demands, but how different facets of these functions are precisely regulated is not fully understood. N6-methyladenosine (m6A) mRNA methylation has emerged as an important mode of epitranscriptional gene expression regulation affecting many biological processes. We show that deleting the m6A methyltransferase, Mettl3, from the adult hematopoietic system led to an accumulation of HSCs in the bone marrow and marked reduction of HSC reconstitution potential due to a blockage of HSC differentiation. Interestingly, deleting Mettl3 from myeloid cells using Lysm-cre did not have any discernable impact on myeloid cell number or function. m6A sequencing on purified HSCs revealed 2,073 genes with significant m6A modification. In particular, Myc, a key regulator of HSC differentiation, was identified as a direct target of m6A in HSCs. Mettl3-deficient HSCs failed to up-regulate Myc expression upon stimulation to differentiate and enforced expression of Myc rescued differentiation defects of Mettl3-deficient HSCs. Our results thus revealed a key role of m6A in governing HSC differentiation by regulating Myc expression. This data includes RNA-Seq analysis to showing only minor gene expression changes in adult bone marrow murine hematopoietic stem cells 10 days after Mettl3 deletion by pIpC administration compared to pIpC treated controls.

2019-03-31 | GSE123526 | GEO

Differentially expressed genes in Mettl3-deficient livers compared to control livers

Project description:Differentially expressed genes in Mettl3-deficient livers compared to control livers

| PRJNA812058 | ENA

Differentially expressed genes in Mettl3-deficient livers compared to control livers

Project description:Liver-specific deficiency of Mettl3 causes liver injury. By performing RNA sequencing (RNA-seq) analysis on the Mettl3-deficient versus control livers, we identified the potential target genes that were closely associated with the liver phenotype in liver-specific Mettl3 knockout mice. RNA-seq analysis revealed extensive metabolic reprogramming in Mettl3-deficient livers. These results demonstrated that Mettl3 coordinates metabolic homeostasis and functional maturation during postnatal liver development.

2022-03-09 | GSE197800 | GEO

Genes differentially expressed in long-term hematopoietic stem cells with latexin deletion

Project description:Genes differentially expressed in long-term hematopoietic stem cells with latexin deletion

| PRJNA371777 | ENA

Multi-omics analysis of hematopoietic progenitors in the fetal liver of Mettl3 deficient mice

Project 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

2020-06-01 | GSE148882 | GEO

mRNA-Seq identifies the differentially expressed mRNA in negative control and METTL3 knockdown HULEC-5a

Project description:mRNA-Seq identifies the differentially expressed mRNA in negative control and METTL3 knockdown HULEC-5a

| PRJNA825718 | ENA

Mettl3-dependent m6A targets in adult murine hematopoietic stem cells

Project description:Hematopoietic stem cells (HSCs) maintain balanced self-renewal and differentiation according to physiological demands, but how different facets of these functions are precisely regulated is not fully understood. N6-methyladenosine (m6A) mRNA methylation has emerged as an important mode of epitranscriptional gene expression regulation affecting many biological processes. We show that deleting the m6A methyltransferase, Mettl3, from the adult hematopoietic system led to an accumulation of HSCs in the bone marrow and marked reduction of HSC reconstitution potential due to a blockage of HSC differentiation. Interestingly, deleting Mettl3 from myeloid cells using Lysm-cre did not have any discernable impact on myeloid cell number or function. m6A sequencing on purified HSCs revealed 2,073 genes with significant m6A modification. In particular, Myc, a key regulator of HSC differentiation, was identified as a direct target of m6A in HSCs. Mettl3-deficient HSCs failed to up-regulate Myc expression upon stimulation to differentiate and enforced expression of Myc rescued differentiation defects of Mettl3-deficient HSCs. Our results thus revealed a key role of m6A in governing HSC differentiation by regulating Myc expression. This data includes m6A sequencing data on HSCs from wild-type or Mettl3-deficient mice, revealing the Mettl3-depedent m6A targets in HSCs.

2019-03-31 | GSE123525 | GEO

Differentially expressed miRNAs in colorectal cancer

Project description:Differentially expressed miRNAs in colorectal cancer

| PRJNA658901 | ENA

Differentially expressed genes following ARID1A depletion

Project description:Differentially expressed genes following ARID1A depletion

| PRJNA477786 | ENA

mRNA-Seq identifies the differentially expressed mRNA in negative control and METTL3 knockdown HULEC-5a

Project description:To identify the molecular mechanism by which METTL3 regulates endothelial barrier function, we performed RNA-seq and MeRIP-seq in HULEC-5a cells with stable METTL3 knockdown and control cells. The RNA-seq results revealed that 437 transcripts were significantly downregulated (fold change <0.5) after METTL3 knockdown. The MeRIP-seq results revealed that the m6A peaks in 1011 transcripts were decreased in abundance (fold change >1.2). Intriguingly, 55 transcripts overlapped in the RNA-seq and MeRIP-seq data

2022-05-20 | GSE200649 | GEO

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