GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE279nnn/GSE279020/primaryOK200OtherMus musculusOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE279020GEOGSEfalsem6A-eCLIP sequencing in mouse alpha cell line aTC1-6 cells with Scramble or Mettl14 KDN6-methyladenosine (m6A) is a widespread RNA modification that plays a crucial role in regulating gene expression, affecting processes such as RNA stability, splicing, and translation. I Previous studies have shown that m6A is involved in fine-tuning β-cell function, but its impact on α-cells, which secrete glucagon in response to low glucose and amino acids, has not been fully investigated. Here, we show that METTL14, a key m6A writer, is essential for maintaining α-cell function and identity. Using a combination of in vitro and in vivo models, we demonstrate that metabolic stimuli such as low glucose and amino acids upregulate METTL14, enhancing glucagon secretion, while insulin downregulates it. Importantly, α-cell-specific knockout of Mettl14 in mice results in impaired glucagon secretion, increased insulin levels, and a surprising conversion of α-cells into β-cells. These findings reveal that m6A is a critical regulator of α-cell identity and function, expanding our understanding of RNA modifications in islet biology. By uncovering a role for METTL14 in maintaining α-cell integrity, our study opens new avenues for exploring RNA-based therapies in diabetes and other metabolic disorders.2026/07/08GSE279020GSM8559707GSM8559708GSM8559703GSM8559704GSM8559705GSM8559706GSM8559701GSM855970230172279020Mus musculus