Nyquist Sarah Kate, Annepureddy Laasya Devi, Sejane Kristija, Furst Annalee, Trahan G Devon, Rudolph Michael C, Twigger Alecia-Jane, Bode Lars, Engelhardt Barbara E, Martin Carli Jayne F, Goods Britt Anne
Gladstone Institute of Data Science & Biotechnology, San Francisco, CA 94158, USA.
Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.
iScience. 2025 Aug 7;28(9):113269. doi: 10.1016/j.isci.2025.113269. eCollection 2025 Sep 19.
Human milk oligosaccharides (HMOs) are integral to infant health. Yet, their complex biosynthesis pathways in the mammary gland during lactation remain under-characterized. To address this knowledge gap, we performed integrated analyses of single-cell RNA-sequencing (scRNA-seq) datasets combined with select HMO concentration measures. We identify differential expression patterns of known HMO synthesis genes in epithelial subsets and nominate several candidate genes that vary with HMO concentration. Additionally, we identify novel gene patterns and transcription factors that may regulate the expression of HMO biosynthesis genes and the cellular pathways supporting HMO production. Finally, we demonstrate that co-expression of HMO synthesis genes and milk fat synthesis genes is limited, suggesting that distinct epithelial cell subtypes may be responsible for the production of different milk components. Our study suggests that HMO synthesis may be achieved through cell-type specialization within the lactocyte compartment.
人乳寡糖（HMOs）对婴儿健康至关重要。然而，它们在哺乳期乳腺中的复杂生物合成途径仍未得到充分表征。为了填补这一知识空白，我们结合选定的HMO浓度测量值，对单细胞RNA测序（scRNA-seq）数据集进行了综合分析。我们确定了上皮亚群中已知HMO合成基因的差异表达模式，并提名了几个随HMO浓度变化的候选基因。此外，我们还确定了可能调节HMO生物合成基因表达以及支持HMO产生的细胞途径的新基因模式和转录因子。最后，我们证明HMO合成基因和乳脂肪合成基因的共表达是有限的，这表明不同的上皮细胞亚型可能负责不同乳成分的产生。我们的研究表明，HMO合成可能通过乳腺上皮细胞内的细胞类型特化来实现。
