Deciphering single-cell landscape unravels cell-type-specific functional roles of RNA mA modification in atherosclerosis.

: Atherosclerosis is a chronic inflammatory disease that is the major cause of mortality worldwide. Although several studies have assessed the function of mA (N-methyladenosine) modification in atherosclerosis, its regulatory mechanism at the single-cell level remains unclear. This study provides a comprehensive single-cell atlas of mA modification regulating cell-type-specific functions in atherosclerosis. : We analyzed single-cell sequencing data derived from atherosclerosis patients to elucidate the influence of mA modification on diverse cell types. We demonstrated the potential regulatory functions of mA regulators across various cell types and key transcription factors involved. Furthermore, we discovered mA regulators mediated intercellular communication in important biological processes. experiments were conducted to further investigate the effects of ALKBH5, WTAP and METTL3 on atherosclerosis. : upregulated in endothelial cells induced cell proliferation and migration involved in sprouting angiogenesis. In smooth muscle cells, upregulation of enhanced proliferation, migration and phenotypic transformation. Upregulation of and promoted macrophage activation and differentiation. Furthermore, we identified abnormally activated transcription factors could regulate mA regulators in a cell-type-specific manner. Moreover, we revealed that mA regulators were implicated in dysregulated intercellular communication in atherosclerosis. And a series of experimental validations supported the conclusion that mA regulators exert cell-type-specific regulatory functions. : Our study provided evidence for the roles of ALKBH5, WTAP and METTL3 in orchestrating atherosclerotic cell-type-specific functions, representing promising targets for precision medicine.