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Published on: February 8, 2013
Single-cell and spatial analyses reveal a tradeoff between murine mammary proliferation and lineage programs
G Kenneth Gray1, Nomeda Girnius2, Hendrik J Kuiken1
1Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Insights
Researchers discovered diverse murine mammary epithelial cell subtypes linked to puberty, estrous cycle, and sex. Endocrine control suppresses lineage programs during mammary gland expansion, particularly during progesterone-dominant periods.
Area of Science:
- Reproductive biology
- Cellular and molecular biology
- Endocrinology
Background:
- Mammary gland epithelial cells exhibit heterogeneity, but endocrine control of this diversity during development is not fully understood.
- Previous studies have identified distinct cell types, yet the extent of subtype variation and its regulation remain unclear.
Purpose of the Study:
- To define murine mammary epithelial cell subtypes and their association with developmental and cyclical changes.
- To investigate the impact of endocrine signaling on mammary epithelial heterogeneity and lineage programming.
Main Methods:
- Utilized mass cytometry and cyclic immunofluorescence to analyze murine mammary epithelial cells.
- Integrated protein and RNA level data to identify cell subtypes and their regulatory mechanisms.
Main Results:
- Identified a rich array of mammary epithelial cell subtypes associated with puberty, estrous cycle, and sex.
- Observed differential proliferation and spatial segregation of these subtypes in pubescent versus adult glands.
- Found systematic suppression of lineage programs at both protein and RNA levels during mammary epithelial expansion.
- Discovered enrichment of ribosomal protein genes in luminal cells during progesterone-dominant periods.
Conclusions:
- The study expands the understanding of murine mammary epithelial heterogeneity.
- Connects endocrine-driven epithelial expansion with lineage suppression, particularly during key reproductive stages.
Abstract:
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.
