Single-cell and spatial analyses reveal a tradeoff between murine mammary proliferation and lineage programs associated with endocrine cues

Although distinct epithelial cell types have been distinguished in glandular tissues such as the mammary gland, the extent of heterogeneity within each cell type and the degree of endocrine control of this diversity across development are incompletely understood. By combining mass cytometry and cycl...

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Bibliographic Details
Published in:Cell reports (Cambridge) Vol. 42; no. 10; p. 113293
Main Authors: Gray, G. Kenneth, Girnius, Nomeda, Kuiken, Hendrik J., Henstridge, Aylin Z., Brugge, Joan S.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 31.10.2023
Elsevier
Subjects:
Animals
cell heterogeneity
Cell Proliferation
CP: Cancer
CP: Developmental biology
Cues
cyclic immunofluorescence
Epithelial Cells - metabolism
mammary gland
Mammary Glands, Animal - metabolism
mass cytometry
Mice
puberty
RNA - metabolism
Spatial Analysis
cell heterogeneity
cyclic immunofluorescence
CP: Cancer
puberty
mammary gland
mass cytometry
CP: Developmental biology
ISSN:2211-1247, 2211-1247
Online Access:Get full text
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Summary:Although distinct epithelial cell types have been distinguished in glandular tissues such as the mammary gland, the extent of heterogeneity within each cell type and the degree of endocrine control of this diversity across development are incompletely understood. By combining mass cytometry and cyclic immunofluorescence, we define a rich array of murine mammary epithelial cell subtypes associated with puberty, the estrous cycle, and sex. These subtypes are differentially proliferative and spatially segregate distinctly in adult versus pubescent glands. Further, we identify systematic suppression of lineage programs at the protein and RNA levels as a common feature of mammary epithelial expansion during puberty, the estrous cycle, and gestation and uncover a pervasive enrichment of ribosomal protein genes in luminal cells elicited specifically during progesterone-dominant expansionary periods. Collectively, these data expand our knowledge of murine mammary epithelial heterogeneity and connect endocrine-driven epithelial expansion with lineage suppression. [Display omitted] •Single-cell analyses identify murine mammary epithelial subtypes•Spatially distinct subtypes are associated with puberty and the estrous cycle•Lineage suppression accompanies proliferative expansion Gray et al. generate a protein and spatial atlas of the murine mammary gland. Distinct epithelial subtypes are associated with puberty, the estrous cycle, and male tissue. Suppression of epithelial lineage programs accompanies endocrine-driven proliferative expansion and de novo structure formation. Progesterone signaling is connected to ribosomal protein gene transcription.
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G.K.G. designed, performed, and analyzed all experiments and datasets. N.G. and A.Z.H. assisted in imaging data acquisition. H.J.K. contributed to marker expression analyses. G.K.G. and J.S.B. conceived this study and wrote the manuscript with input from all the other authors.
AUTHOR CONTRIBUTIONS
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2023.113293