Journal
JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA
Volume 26, Issue 1, Pages 43-66Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10911-021-09486-3
Keywords
Single-cell RNA sequencing; Mammary epithelial lineages; Mammary immune cells; Gene expression; breast epithelial evolution
Categories
Funding
- CSHL Cancer Center Support Grant [5P30CA045508]
- CSHL
- Northwell Health affiliation
- Simons Foundation Award
- Rita Allen Scholar Award
- Pershing Square Sohn Prize for Cancer Research
- NIH/NCI grant [R01CA248158-01]
- NIH/NIA grant [R01 AG069727-01]
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This study improved the definitions of mammary-resident cellular identities at the single-cell level by combining different fractionation methods and transcriptional profiling, revealing the heterogeneity of mammary epithelial cells and the diversity of non-epithelial mammary cells. The research also provided useful molecular signatures for future studies on normal and malignant breast development using single-cell profiling strategies.
The developing mammary gland depends on several transcription-dependent networks to define cellular identities and differentiation trajectories. Recent technological advancements that allow for single-cell profiling of gene expression have provided an initial picture into the epithelial cellular heterogeneity across the diverse stages of gland maturation. Still, a deeper dive into expanded molecular signatures would improve our understanding of the diversity of mammary epithelial and non-epithelial cellular populations across different tissue developmental stages, mouse strains and mammalian species. Here, we combined differential mammary gland fractionation approaches and transcriptional profiles obtained from FACS-isolated mammary cells to improve our definitions of mammary-resident, cellular identities at the single-cell level. Our approach yielded a series of expression signatures that illustrate the heterogeneity of mammary epithelial cells, specifically those of the luminal fate, and uncovered transcriptional changes to their lineage-defined, cellular states that are induced during gland development. Our analysis also provided molecular signatures that identified non-epithelial mammary cells, including adipocytes, fibroblasts and rare immune cells. Lastly, we extended our study to elucidate expression signatures of human, breast-resident cells, a strategy that allowed for the cross-species comparison of mammary epithelial identities. Collectively, our approach improved the existing signatures of normal mammary epithelial cells, as well as elucidated the diversity of non-epithelial cells in murine and human breast tissue. Our study provides a useful resource for future studies that use single-cell molecular profiling strategies to understand normal and malignant breast development.
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