BioProject

Changes in mammary cell behavior mediating normal breast development during pregnancy and lactation are poorly understood due to limited availability of breast biopsies during this time. More...

Changes in mammary cell behavior mediating normal breast development during pregnancy and lactation are poorly understood due to limited availability of breast biopsies during this time. Human milk contains a hierarchy of cells including stem cells, mature milk producing cells (lactocytes) and myoepithelial cells. Here we non-invasively sampled the total epithelial cell population of the lactating mammary gland from mature HM collected from healthy mother/infant dyads during the first year postpartum, and explored temporal changes in the mammary cell transcriptome using RNA sequencing. Comparisons were done with mammary secretions from late pregnancy from the same women and with purchased resting mammary tissue. Distinct gene signatures were found for the different mammary developmental stages examined. Cell adhesion pathways were differentially regulated between the resting gland and pregnancy, whereas immune cell signaling and morphogenesis/cancer pathways differed between lactation and pregnancy or the resting gland, respectively. The transcriptome of lactation remained consistent in the first year postpartum in these successfully lactating women. The gene signatures characteristic of HM cells confirmed lactation genes previously reported in animal models and the HM fat globule. This study identifies key genes and molecular pathways undergoing controlled regulation as the mammary gland transitions from a quiescent into a functional organ, providing experimental targets for the molecular investigation of mammary gland pathologies. Overall design: The human milk cell transcriptome was generated from cells extracted from pre-partum samples and mature milk at months 1, 3, 6 and 12 of lactation. Less...