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Effects of depletion of Nat10 on gene expression from bone marrow derived cell

ABSTRACT: N4-acetylcytidine (ac4C), a form of RNA acetylation catalyzed by N-acetyltransferase 10 (Nat10), acts as a post-transcriptional regulator of RNA function. However, its role in immune cell function and ulcerative colitis (UC) remains poorly understood. Here, single-cell RNA sequencing revealed a significant downregulation of Nat10 expression in macrophages from UC, which negatively correlated with disease progression. Conditional deletion of Nat10 in murine macrophages impaired their proliferative capacity without affecting apoptosis, thereby exacerbating dextran sulfate sodium (DSS)-induced colitis. Subsequent transcriptomic analysis identified widespread dysregulation of cell cycle-related genes, with minichromosome maintenance complex component 2 (Mcm2) identified as a direct target of Nat10-mediated ac4C modification. Loss of Nat10 led to accelerated Mcm2 mRNA degradation, resulting in reduced Mcm2 protein levels, whereas overexpression of Mcm2 in Nat10-deficient macrophages restored their proliferative capacity. Moreover, Nat10-deficient macrophages exhibited diminished ability to support intestinal epithelial cell growth and self-renewal. Collectively, this study provides the first in vivo evidence that Nat10-mediated ac4C modification sustains macrophage proliferative, attenuating colitis progression through stabilization of Mcm2 mRNA. This work uncovers a novel Nat10–ac4C–Mcm2 axis and highlights its potential as a therapeutic target in UC.

ORGANISM(S): Mus musculus

PROVIDER: GSE305465 | GEO | 2026/08/31

REPOSITORIES: GEO

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