Journal
NATURE COMMUNICATIONS
Volume 8, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-017-01560-x
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Funding
- Australian National Health and Medical Research Council (NHMRC) [1016701, 1054618, 1100807, 1113133]
- NHMRC IRIISS
- Victorian State Government through VCA of Victorian Breast Cancer Research Consortium and Operational Infrastructure Support
- Australian Cancer Research Foundation
- Ian Potter Foundation
- National Breast Cancer Foundation (NBCF)
- NHMRC [1078730, 1058892, 1037230, 1102742]
- National Health and Medical Research Council of Australia [1102742, 1100807, 1078730, 1058892] Funding Source: NHMRC
- National Breast Cancer Foundation [ECF-14-043] Funding Source: researchfish
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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.
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