Genetic characterization of human milk production

Between five to fifteen percent of lactating mothers experience chronic low milk supply and cannot produce enough milk to support their infant’s growth. Regardless of the high prevalence of this condition, there are no available diagnostic tools or treatment protocols and very little is known about human milk production in general and specifically about challenges associated with breastfeeding at the molecular level.

By carrying out various genomic analyses on fresh human milk samples from lactating women, with low, normal, or high milk supply we are characterizing changes in gene expression in the mammary gland that influence human milk production. We performed RNA-seq (mRNA and lncRNA) on the milk fat layer and found a subset of genes to be significantly differentially expressed between high and low milk producers. In addition, single cell RNA-seq (scRNA-seq) analysis revealed six main cell populations in human milk and found that individuals with low milk supply have smaller fraction of LC2 secretory cells compared to high suppliers. Furthermore, we analyse nineteen types of human milk oligosaccharides (HMOs) in 33 samples and correlate their levels with maternal gene expression in the mammary gland, as well as with the milk and infant microbiome. In addition, using scRNA-seq we are characterizing changes in milk cell populations after immunization and infection (with SARS-CoV-2), allowing us to better understand the mucosal immune response under these states.

Together, findings from this study will improve our understanding of human milk production and mammary gland function during lactation at the cellular and molecular level.