Zheng Weijie, Zhang Junnan, Huang Jinfeng, Han Bo, Liu Yanan, Sun Dongxiao
Department of Animal Genetics and Breeding, College of Animal Science and Technology, Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, State Key Laboratory of Animal Biotech Breeding, China Agricultural University, Beijing, China.
Department of Agriculture and Rural Affairs of Guangdong Province, Guangzhou, China.
Commun Biol. 2025 Aug 4;8(1):1150. doi: 10.1038/s42003-025-08615-6.
Milk protein percentage (PP) and fat percentage (FP) are important indicators for measuring milk quality, but only a few causative genes such as DGAT1, GHR, and ABCG2, have been identified, indicating substantial potential for further exploration. Here, we integrated genotyping, RNA-seq, ATAC-seq, single-cell atlas and cis-QTLs datasets from the liver and mammary gland to investigate their genetic regulation. We identified cell type affecting milk composition, such as HPE2 and LumSec-HSPH1, and highlighted nine candidate genes (EFNA1, ERBB3, DUSP16, DEPTOR, TRIM46, HSTN, CIDEA, ACACA and SPP1) that are involved in the regulation of milk protein and fat synthesis through MAPK, AMPK, PI3K-Akt, and mTOR signalling pathways. Notably, EFNA1 was consistently identified across all omics analyses, showing increased promoter accessibility in the high PP group, potentially driven by CTCF and RXRA-mediated transcriptional activation. Overall, this study reveals potential cell types, candidate genes, and regulatory mechanisms influencing milk composition, offering insights to support milk quality improvement. The limited sample size represents the main constraint of this work, and future efforts will focus on population-scale genetic analyses and wet-lab validation.
乳蛋白率（PP）和乳脂率（FP）是衡量牛奶品质的重要指标，但目前仅鉴定出少数几个致病基因，如DGAT1、GHR和ABCG2，这表明仍有很大的进一步探索潜力。在此，我们整合了来自肝脏和乳腺的基因分型、RNA测序、ATAC测序、单细胞图谱和顺式QTL数据集，以研究它们的遗传调控。我们鉴定出了影响牛奶成分的细胞类型，如HPE2和LumSec-HSPH1，并突出了九个候选基因（EFNA1、ERBB3、DUSP16、DEPTOR、TRIM46、HSTN、CIDEA、ACACA和SPP1），这些基因通过MAPK、AMPK、PI3K-Akt和mTOR信号通路参与乳蛋白和脂肪合成的调控。值得注意的是，在所有组学分析中均一致鉴定出EFNA1，其在高PP组中启动子可及性增加，这可能是由CTCF和RXRA介导的转录激活所驱动。总体而言，本研究揭示了影响牛奶成分的潜在细胞类型、候选基因和调控机制，为支持牛奶品质改善提供了见解。样本量有限是这项工作的主要限制因素，未来的工作将集中在群体规模的遗传分析和湿实验室验证上。
