Lion-head goose is a large-sized breed native to Guangdong Province, China, exhibits remarkable capacity for fatty liver production under overfeeding conditions and is highly valued by local farmers and consumers. However, the molecular mechanisms driving fatty liver development in this breed are still unknown. In this study, we evaluated liver weight differences between normally fed and overfed Lion-head geese and further examined sex-specific differences following overfeeding. Overfeeding significantly increased liver weight more than 340%, and males possess a stronger capacity for lipid deposition under the same feeding regimen compared with females. RNA-Seq analysis identified 1476 differentially expressed genes (DEGs) shared by both sexes, which were mainly enriched in lipid and energy metabolism, oxidative stress, and mitochondrial pathways. In addition, 627 male-specific and 420 female-specific DEGs revealed sex-dependent differences, with males showing stronger transcriptional regulation and females exhibiting enhanced antioxidant and detoxification responses. Weighted gene co-expression network analysis (WGCNA) revealed 320 co-hub genes enriched in lipid and energy metabolism in overfeeding-induced fatty liver, along with 9 co-hub genes related to sex differences. Alternative splicing (AS) analysis detected 131 differentially spliced genes (DSGs). Integration of both approaches identified 7 overlapping genes, HYCC2 (Hyccin PI4KA lipid kinase complex subunit 2), AGL (Amylo-Alpha-1,6-Glucosidase and 4-Alpha-Glucanotransferase), CCDC62 (Coiled-coil domain containing 62), IGSF5 (Immunoglobulin superfamily member 5), MGARP (Mitochondria-localized glutamic acid-rich protein), CD80 (Cluster of Differentiation 80), and FPGS (Folylpolyglutamate synthase), as potential key regulators. These findings provide new insights into transcriptional and post-transcriptional regulation of overfeeding-induced fatty liver in geese.

As a type of cell with self-renewal ability and multi-directional differentiation potential, stem cells are closely related to their functions, such as reprogramming transcription factors, histone modifications, and energy metabolism. m⁶A (N⁶-methyladenosine modification) is one of the most abundant modifications in RNA, and dynamic reversible m⁶A modification plays an important role in regulating stem cell function. This review moves beyond listing isolated functions and instead adopts an integrated perspective, viewing m⁶A as a temporal regulator of cellular state transitions. We discuss how m⁶A dynamically regulates stem cell pluripotency, coordinates epigenetic and metabolic reprogramming, and serves as a central hub integrating key signaling pathways (Wnt, PI3K-AKT, JAK-STAT, and Hippo). Finally, using somatic reprogramming as an example, we elucidate the stage-specific role of m⁶A in complex fate transitions. This comprehensive exposition not only clarifies the context-dependent logic of m⁶A regulation but also provides a precise framework for targeting the m⁶A axis in regenerative medicine and cancer therapy.