Cell type and stage specific transcriptional, chromatin and cell-cell communication landscapes in the mammary gland

Abstract

The mammary gland (MG) is composed of three main epithelial lineages, the basal cells (BC), the estrogen receptor (ER) positive luminal cells (ER+ LC), and the ER negative LC (ER− LC). Defining the cell identity of each lineage and how it is modulated throughout the different stages of life is important to understand how these cells function and communicate throughout life. Here, we used transgenic mice specifically labelling ER+ LC combined to cell surface markers to isolate with high purity the 3 distinct cell lineages of the mammary gland and defined their expression profiles and chromatin landscapes by performing bulk RNAseq and ATACseq of these isolated populations in puberty, adulthood and mid-pregnancy. Our analysis identified conserved genes, ligands and transcription factor (TF) associated with a specific lineage throughout life as well as genes, ligands and TFs specific for a particular stage of the MG. In summary, our study identified genes and TF network associated with the identity, function and cell-cell communication of the different epithelial lineages of the MG at different stages of life.

Keywords

• Mammary gland
• Cell lineage
• Cell identity
• Gene regulatory network
• Life stages