Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Expression profiling of METTL14 depleted human pancreatic β-like cells

ABSTRACT: N6-methyladenosine (m6A) is the most abundant chemical modification in mRNA, and plays important roles in human embryonic stem cell pluripotency, maintenance, and differentiation. However, the role of m6A and the precise mechanisms involved during the development of β-cells are unexplored. Here, we explored the requirement of METTL14-mediated m6A RNA methylome in human pancreatic β-like cells by simultaneously inducing METTL14 knockdown in H1 human embryonic stem cells (hESCs) with doxycycline (Dox) treatment and differentiating hESCs towards pancreatic β-like cells in vitro.

ORGANISM(S): Homo sapiens

PROVIDER: GSE236323 | GEO | 2024/06/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Expression profiling of METTL14 depleted human embryoid bodies

Project description:N6-methyladenosine (m6A) is the most abundant chemical modification in mRNA, and plays important roles in human embryonic stem cell pluripotency, maintenance, and differentiation. However, the role of m6A and the precise mechanisms involved during the development of β-cells are unexplored. Here, we explored the requirement of METTL14-mediated m6A RNA methylome in human embryonic stem cell (hESC) differentiation by simultaneously inducing METTL14 knockdown in H1 and MEL1 hESCs with doxycycline (Dox) treatment and differentiating hESCs towards the three embryonic germ layers using embryoid body (EB) formation assays.

2024-07-01 | GSE236322 | GEO

N6-methyladenosine profiling of differentiating human pancreatic β-cells in vitro

Project description:N6-methyladenosine (m6A) is the most abundant chemical modification in mRNA, and plays important roles in human embryonic stem cell pluripotency, maintenance, and differentiation. However, the role of m6A and the precise mechanisms involved during the development of β-cells are unexplored. Here, we differentiated human embryonic stem cells (hESCs) into pancreatic β-like cells and performed RNA-Seq and m6A-seq at different stages of in vitro β-like cell differentiation.

2024-06-13 | GSE236325 | GEO

Adipose METTL14-elicited N6-methyladenosine promotes obesity, insulin resistance, and NAFLD by suppressing β adrenergic signaling and lipolysis

Project description:Obesity is associated with impaired β-adrenergic receptor (Adrb1-3) signaling and lipolysis, leading to aberrant white adipose tissue (WAT) growth. WAT research has been centered on transcriptional and posttranslational regulations, but posttranscriptional regulation and mRNA modifications are poorly understood. Here, we unveil a METTL14/N6-methyladenosine (m6A) paradigm guiding β-adrenergic signaling and lipolysis. METTL14 complex installs m6A on RNA, regulating mRNA fate and translation. We found that feeding and insulin increased adipose Mettl14 and m6A levels. Adipose Mettl14 and m6A were upregulated in high fat diet (HFD)-induced obesity. Ablation of adipose Mettl14 decreased Adrb2, Adrb3, Atgl (encoding lipase), and Cig-58 (Atgl activator) transcript m6A contents while increasing their translation and protein levels, thereby enhancing adipose β-adrenergic signaling and lipolysis. Consequently, adipocyte-specific Mettl14 knockout mice were resistant to HFD-induced obesity, insulin resistance, glucose intolerance, and NAFLD. These results unravel a METTL14/m6A-based epitranscriptomic mechanism governing β-adrenergic signaling, lipolysis, and adipose growth in health and disease.

2023-06-04 | GSE233782 | GEO

Arginine methylation of METTL14 promotes RNA N6-methyladenosine modification

Project description:Both mRNA and proteins can be modified through addition of methyl groups. For example, addition of N6-methyladenosine (m6A) to mRNAs is critical for human development and health. Post-translational methylation of proteins can impact the dynamic regulation of enzymatic activity. Here we sought to explore the nexus of transcriptional and post-translational methylation by studying the role of methylation of the core methyltransferase METTL3/METTL14 in m6A regulation. We found by mass spectrometry that METTL14 arginine 255 (R255) is methylated (R255me). Global mRNA m6A levels were greatly decreased in METTL14 R255K mutant mouse embryonic stem cells (mESCs). We further found that R255me greatly enhances the interaction of METTL3/METTL14 with WTAP and promotes the binding of the complex to substrate RNA.

2021-05-14 | GSE164047 | GEO

Phospho-antibody microarray analyses for islets of control and Mettl14 knock-out mice

Project description:β-cell specific Mettl14 knock-out mice display reduced N6-methyladenosine (m6A) levels and recapitulate human Type II diabetes (T2D) islet phenotype with early diabetes onset and mortality secondary to decreased β-cell proliferation and insulin degranulation. To gain insights into the role of m6A in regulating the IGF1/insulin -> AKT - > PDX1 pathway and to dissect the signaling networks modulating AKT phosphorylation, we subjected freshly isolated islets from control and Mettl14 knock-out mice to phospho-antibody microarrays.

2019-08-09 | GSE132111 | GEO

Primarily Dissecting the Autonomous and Cooperative Functions of METTL3 and METTL14 in mRNA Modification and Tumor Progression

Project description:METTL3 and METTL14 are considered to faithfully form the m6A writing complex in a 1:1 ratio, regulating the fate of mRNA by adding m6A modifications. However, recent studies have shown inconsistent expression and prognostic value of METTL3 and METTL14 in some tumors, suggesting that they may not be faithful in tumors. Pan-cancer analysis based on TCGA data reveals significant differences in expression, function, tumor burden correlation, and immune correlation between METTL3 and METTL14, especially in esophageal squamous cell carcinoma (ESCC). Knockdown of METTL3 significantly inhibits the cell proliferation in vitro and in vivo in ESCC EC109 cells, while the impact of METTL14 knockdown on proliferation is limited, and it cannot abolish the expression of METTL3 protein. mRNA-seq results indicate that METTL3 independently regulates the expression of 1615 genes, while only 776 genes are co-regulated by METTL3 and METTL14. Furthermore, through immunofluorescence co-localization, it is observed that METTL3 and METTL14 have certain inconsistencies in cellular localization. HPLC-MS results show that METTL3 independently binds to the Nop56p-associated pre-rRNA complex and mRNA splicing complex, separate from METTL14. Through bioinformatics and various omics studies, we have preliminarily discovered that METTL3 independently regulating tumor cell proliferation, and the participation in mRNA splicing may be a critical molecular mechanism. Our study provides an experimental basis and theoretical foundation for further understanding of the m6A writing complex and tumor therapy targeting METTL3.

2024-02-01 | PXD048886 | Pride

METTL14 is a chromatin regulator independent of RNA N6-methyladenosine (mRNA)

Project description:METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC, also known as m6A writer) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on mouse embryonic stem cell (mESC) self-renewal. While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-indenepent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification and PRC2 complex. Mechanically, METTL14, but not METTL3, recognizes H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression . The regulation of H3K27me3 by METTL14 is essential to the transition of mESCs from self-renewal to differentiation. This work reveals a regulation mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance and differentiation of mESCs.

2024-08-16 | GSE183400 | GEO

Mettl14 is required for mouse postimplantation development by facilitating epiblast maturation

Project description:N6-methyladenosine (m6A) is the most prevalent and reversible internal modification of mammalian messenger and noncoding RNAs mediated by specificm6A writer, reader, and eraser proteins. As an m6A writer, the methyltransferase-like 3-methyltransferase–like 14 (METTL14)–Wilms tumor 1–associated protein complex dynamically regulates m6A modification and plays important roles in diverse biologic processes. However, our knowledge about the complete functions of this RNA methyltransferase complex, the contributions of each componenttothemethylation, andtheir effects on different biologicpathways are still limited. By using both in vivo and in vitro models, we here report that METTL14 is indispensable for postimplantation embryonic development by facilitating the conversion from naive to primed state of the epiblast. Depletion of Mettl14 leads to conspicuous embryonic growth retardation from embryonic d 6.5, mainly as a result of resistanceto differentiation, which further leads to embryonic lethality early in gestation. Our data highlight the critical function of METTL14 as an m6A modification regulator in orchestrating early mouse embryogenesis.

2020-12-10 | GSE162906 | GEO

Arginine methylation of METTL14 promotes RNA N6-methyladenosine modification and endoderm differentiation of mouse embryonic stem cells

Project description:m6A is the most abundant modification of mRNA in mammals and plays an important role in human development and disease. METTL14 is a key component of m6A methyltransferase complex. The project showed that its post-translational arginine methylation can regulate the generation of m6A and the endoderm differentiation of mouse embryonic stem cells, indicating its essential function in the normal development of embryos.

2021-05-17 | PXD018458 | iProX