Journal Article

Construction of developmental lineage relationships in the mouse mammary gland by single-cell RNA profiling

Visvader, Jane E., Gordon, Lavinia, Chen, Yunshun, Wilcox, Stephen, Pal, Bhupinder, Lindeman, Geoffrey J., Smyth, Gordon K., Jamieson, Paul, Liu, Kevin He, Rios, Anne C., Davis, Melissa J., Jackling, Felicity C., Fu, Naiyang, Vaillant, François

2017

Overview

The mammary epithelium comprises two primary cellular lineages, but the degree of heterogeneity within these compartments and their lineage relationships during development remain an open question. Here we report single-cell RNA profiling of mouse mammary epithelial cells spanning four developmental stages in the post-natal gland. Notably, the epithelium undergoes a large-scale shift in gene expression from a relatively homogeneous basal-like program in pre-puberty to distinct lineage-restricted programs in puberty. Interrogation of single-cell transcriptomes reveals different levels of diversity within the luminal and basal compartments, and identifies an early progenitor subset marked by CD55. Moreover, we uncover a luminal transit population and a rare mixed-lineage cluster amongst basal cells in the adult mammary gland. Together these findings point to a developmental hierarchy in which a basal-like gene expression program prevails in the early post-natal gland prior to the specification of distinct lineage signatures, and the presence of cellular intermediates that may serve as transit or lineage-primed cells. The mammary epithelium comprises two cell lineages but the heterogeneity amongst these during development is unclear. Here, the authors report single-cell RNA sequencing of the mouse mammary epithelium at four developmental stages, revealing diversity in both compartments and a transcriptional shift with puberty onset.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/136/2060 / 631/337/2019 / 631/80 / Animals / Basal cells / CD55 Antigens - genetics / CD55 Antigens - metabolism / Cell Lineage / Compartments / Developmental stages / Epithelial cells / Epithelial Cells - metabolism / Epithelium / Female / Gene expression / Gene Expression Profiling / Heterogeneity / Humanities and Social Sciences / Intermediates / Interrogation / Mammary gland / Mammary Glands, Animal - cytology / Mammary Glands, Animal - growth & development / Mammary Glands, Animal - metabolism / Mice / multidisciplinary / Puberty / Ribonucleic acid / RNA / RNA - genetics / RNA - metabolism / Rodents / Science / Science (multidisciplinary) / Single-Cell Analysis / Transcriptome