The precise timing of lineage commitment, however, remains an area of investigation. While chromatin accessibility analysis has indicated multilineage potential in both fetal and adult basal/myoepithelial mammary cells, recent single-nucleus ATAC-seq profiling revealed the presence of cells with either luminal or basal-oriented chromatin structure before birth. Lineage specification has been inferred to occur after birth, based on scRNA-seq analysis of the early developing mouse mammary gland. Single cell (sc) RNA-seq analysis of epithelial cells isolated during pregnancy has uncovered uni-lineage clusters as well as a mixed-lineage subset. Equivalent populations have been observed in human breast epithelium by single cell transcriptomics. Analysis of the adult gland revealed three major epithelial subsets corresponding to the basal, luminal progenitor (LP also referred to as secretory), and mature luminal (ML also referred to as hormone-responsive) populations, consistent with cell sorting studies. Recent transcriptional mapping studies at the single cell level have shed light on heterogeneity within the different epithelial populations in the mouse mammary gland and potential spatio-temporal relationships. Structurally, the epithelium of the ductal tree is bilayered and comprises an inner layer of luminal cells and an outer layer of myoepithelial cells that directly contact the underlying basement membrane. The final process of involution entails large-scale cell death of alveolar units and remodeling of the gland to its prepregnant state.

Pregnancy is accompanied by the prolific expansion of alveoli that emanate from the branches and constitute the milk-producing units to enable lactation. This process is driven by terminal end buds (TEBs), which are located at the termini of the growing ducts. During puberty, the ductal tree elongates and bifurcates to form an extensive ductal network that fills the mammary fat pad. The majority of development, however, occurs in the postnatal animal. At E13.5, a bud forms via invagination of the mesenchyme these buds sprout by E15.5 and form a lumen, and by E18.5, a small arborized ductal structure has invaded the mammary fat pad. During embryonic development, mammary morphogenesis initiates from the ectoderm at E10.5, giving rise to 5 pairs of placodes by E11.5. The mammary epithelium undergoes remarkable remodeling during the different stages of postnatal morphogenesis. The Creative Commons Public Domain Dedication waiver ( ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

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