Single cell RNA-seq reveals heterogeneity and hierarchy of mouse mammary epithelia

The mammary epithelia are mainly composed of two distinct lineages, the basal and luminal cells. Due to the limitation of traditional transcriptome analysis of bulk mammary cells, the hierarchy and heterogeneity of mammary cells within these two lineages remain unclear. Hence, we have performed single cell RNA-seq on mammary epithelial cells of virgin and pregnant mice. Based on the respective gene expression profiles, we found mammary cells are highly heterogeneous and can be classified into distinct subgroups with signature markers. Besides, we identified and verified a rare CDH5+ subpopulation of basal lineage as quiescent mammary gland stem cells (MaSCs). Furthermore, knockout of Cdh5 in mouse mammary cells via CRISPR-Cas9 significantly impairs cell stemness and promotes the cell differentiation to luminal lineage. In addition, via pseudo-temporal analysis, we reconstructed the mammary epithelia developmental trajectory and revealed the relevant changes of gene expression and biological functions of mammary cells along the developmental process. Overall design: Basal and luminal cells form mammary glands of virgin or pregnant (at day 12) FVB mice were FACS-purified for single cell RNA-seq.

482

Sun H, Miao Z, Zhang X, Chan UI, Su SM, Guo S, Wong CKH, Xu X, Deng CX