Comprehensive Identification of the Bovine KLF Gene Family and Its Functional Regulation in Muscle Development: Insights from Single-Nuclei Transcriptomics

The Krüppel-like factor (<i>KLF</i>) family of transcription regulators plays pivotal roles in adipogenesis, myogenesis, and metabolism. While comprehensively studied in humans and mice, its characterization in cattle remains limited, especially within the skeletal muscle niche. This study aimed to systematically characterize the <i>KLF</i> family in Bos taurus and elucidate its role in breed-specific muscular development. We employed an integrated approach of comparative genomics and single-nucleus RNA sequencing (snRNA-seq) on longissimus dorsi muscle from Angus (ANG, beef breed) and Holstein (HST, dairy breed) cattle. Phylogenomic analysis identified 14 <i>KLF</i> genes, revealing evolutionary conservation and potential functional divergence. snRNA-seq delineated 11 distinct cell populations and uncovered cell-type-specific expression patterns of <i>KLFs</i>. Further machine learning based analysis pinpointed <i>KLF6</i>, <i>KLF9</i>, <i>KLF10</i>, and <i>KLF12</i> as key global drivers of transcriptional differences between breeds, while <i>KLF6</i> was identified as a major cell-type-specific contributor in lymphatic endothelial cells. Our work provides a foundational resource for understanding the <i>KLF</i> family in cattle and identifies promising candidate genes for improving meat production traits through molecular breeding.