Cow Cell Atlas Paves The Way For Novel Lactation Discoveries

Written by: Alla Katsnelson, Ph.D | Issue # 129 | 2025

A new atlas that maps gene expression of almost 1.8 million cells across 59 tissue types in Holstein cows offers the first comprehensive catalog of bovine cells [1]. The resource, called the Cattle Cell Atlas, gives researchers a cell-type-level view of molecular and genetic information integrated across a variety of biological states. 

“This work is foundational,” says Klaus Lehnert, a professor of genetics and genomics at the University of Auckland and a scientific advisor to the International Milk Genomics Consortium. 

Although the study reports some important and interesting findings, Lehnert says, its main value is not the specific results, but the future discoveries the data will enable.  “It allows others to come along with new hypotheses, to analyze the data and develop other insights,” he says. 

To create the atlas, the team analyzed cells from 15 Holstein calves and adult cows. Using single cell RNA sequencing technology, they identified 131 different cell types and characterized their gene expression patterns. The team then integrated these gene expression profiles with genetic data to link specific cell types to key traits such as milk production and fertility. They also compared immune-related gene markers between cows and humans to identify cell types relevant to the immune conditions. 

Previous work integrating gene expression and other molecular information with gene-level data such as from genome-wide association studies has generally used tissue comprising a mixture of many different cell types from a particular organ, conflating all the different cell types that make up that tissue. [2] However, separating the gene expression profiles based on individual cell types will be a major boon for future studies, Lehnert says, because it will allow researchers to untangle which specific cell types are producing a given biological effect. This approach can also reveal biological insights from rare cells in the tissue that may have been drowned out by signals from more dominant cell types in previous studies. 

One topic poised to get a boost from the Cattle Cell Atlas is the basic physiology of lactation, Lehnert says. The study identified six different secretory cell types in the mammary gland. Only one of them, called ME7 in the study, appears to respond to oxytocin, a key hormone in lactation that enables the initial let-down of milk in mammals.  [3] Studies focusing specifically on ME7 cells can further probe oxytocin mechanisms, while studies of other cell types can identify molecular pathways controlling other aspects of lactation, such as milk yield and fat and protein content.

A closer look at these mammary secretory cells might reveal, for example, whether any of them express genes encoding enzymes called glycosyl transferases, which create special sugar molecules known for their health-promoting benefits in offspring. [4] According to Lehnert, If cows can produce these enzymes even in tiny amounts, it may be possible to develop feeding strategies that boost their levels in cow’s milk, to help make infant formula more like human milk.  

Another interesting finding in the study is that the bovine liver contains specific cell types enriched for lactation-related genes, enabling it to support the high metabolic demands of milk production in dairy cattle. Bovine liver cells were especially enriched in functions such the metabolism of fatty acids, which are necessary for milk production. [5] This makes sense given that cows have been selected for lactation performance for more than 9000 years, Lehnert explains.

Finally, the study identified gene expression similarities between cows and people, particularly in myeloid cells, which are related to immune function. The authors suggest that these parallels could make cattle a model for studying some aspects of human biology. How useful cows are as a model organism for human immunology remains to be seen, explains Lehnert, but the comparison could be valuable in metabolic conditions. “Millions of cows are measured for metabolic performance every year – but it’s not done so much for humans,” he says. Based on the similarities identified, it may be possible to generate some hypotheses about human metabolism. 

References

1. Han B, Li H, Zheng W, Zhang Q, Chen A, Zhu S, Shi T, Wang F, Zou D, Song Y, Ye W, Du A, Fu Y, Jia M, Bai Z, Yuan Z, Liu W, Tuo W, Hope JC, MacHugh DE, O’Grady JF, Madsen O, Sahana G, Luo Y, Lin L, Li C, Cai Z, Li B, Huang J, Liu L, Zhang Z, Ma Z, Hou Y, Liu GE, Jiang Y, Sun HZ, Fang L, Sun D. A multi-tissue single-cell expression atlas in cattle. Nat Genet. 2025; 57(10):2546-2561. 
2. Liu S, Gao Y, Canela-Xandri O, Wang S, Yu Y, Cai W, Li B, Xiang R, Chamberlain AJ, Pairo-Castineira E, D’Mellow K, Rawlik K, Xia C, Yao Y, Navarro P, Rocha D, Li X, Yan Z, Li C, Rosen BD, Van Tassell CP, Vanraden PM, Zhang S, Ma L, Cole JB, Liu GE, Tenesa A, Fang L. A multi-tissue atlas of regulatory variants in cattle. Nat Genet. 2022; 54(9):1438-1447. 
3. Iovino M, Messana T, Tortora A, Giusti C, Lisco G, Giagulli VA, Guastamacchia E, De Pergola G, Triggiani V. Oxytocin Signaling Pathway: From Cell Biology to Clinical Implications. Endocr Metab Immune Disord Drug Targets. 2021; 21(1):91-110.
4. Lairson LL, Henrissat B, Davies GJ, Withers SG. Glycosyltransferases: structures, functions, and mechanisms. Annu Rev Biochem. 2008;77:521-55.
5. Sosa-Castillo E, Rodríguez-Cruz M, Moltó-Puigmartí C. Genomics of lactation: role of nutrigenomics and nutrigenetics in the fatty acid composition of human milk. Br J Nutr. 2017;118(3):161-168. 

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