Abstract
Breastmilk is a rich source of cells with a heterogeneous composition comprising early-stage stem cells, progenitors and more differentiated cells. The gene expression profiles of these cells and their associations with characteristics of the breastfeeding mother and infant are poorly understood. This study investigated factors associated with the cellular dynamics of breastmilk and explored variations amongst women. Genes representing different breastmilk cell populations including mammary epithelial and myoepithelial cells, progenitors, and multi-lineage stem cells showed great variation in expression. Stem cell markers ESRRB and CK5, myoepithelial marker CK14, and lactocyte marker α-lactalbumin were amongst the genes most highly expressed across all samples tested. Genes exerting similar functions, such as either stem cell regulation or milk production, were found to be closely associated. Infant gestational age at delivery and changes in maternal bra cup size between pre-pregnancy and postpartum lactation were associated with expression of genes controlling stemness as well as milk synthesis. Additional correlations were found between genes and dyad characteristics, which may explain abnormalities related to low breastmilk supply or preterm birth. Our findings highlight the heterogeneity of breastmilk cell content and its changes associated with characteristics of the breastfeeding dyad that may reflect changing infant needs.
Highlights
Breastmilk is a rich source of cells with a heterogeneous composition comprising early-stage stem cells, progenitors and more differentiated cells
When testing gene clusters and demographics, we found cell content to be significantly associated with the gene cluster PC1 (α -LA, epithelial cell adhesion molecule (EPCAM), PTEN and NOGGIN) (p < 0.001)
We identified genes such as estrogen-related receptor-β (ESRRB), cytokeratin 5 (CK5), cytokeratin 14 (CK14) and α -lactalbumin (α -LA), which was universally expressed at high levels amongst the breastmilk cell samples examined
Summary
Breastmilk is a rich source of cells with a heterogeneous composition comprising early-stage stem cells, progenitors and more differentiated cells. Genes representing different breastmilk cell populations including mammary epithelial and myoepithelial cells, progenitors, and multi-lineage stem cells showed great variation in expression. Human milk (breastmilk) is a complex fluid consisting of a number of diverse components, which are biologically optimised for the human infant[1] Amongst these are biochemical factors that provide nutrition, immunological support and developmental programming, and which change dynamically both within and between women[2,3,4]. Earlier reports have demonstrated that epithelial cells isolated from freshly expressed breastmilk were able to expand in adherent culture and form colonies of various morphologies that could be maintained through multiple passages[15,18,19,20,21]. These observations together with previous work by Russo et al on the ultra-structure of lactocytes suggested that breastmilk contains both less differentiated, self-renewing cells and more differentiated milk-secretory cells[22]
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