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Updated: Sep 4, 2025
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An Ex vivo Model to Study Hormone Action in the Human Breast
Published on: January 8, 2015
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Mapping hormone-regulated cell-cell interaction networks in the human breast at single-cell resolution
Lyndsay M Murrow1, Robert J Weber2, Joseph A Caruso3
1Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Cell Systems
|July 21, 2022
Summary
Hormones like estrogen and progesterone regulate breast tissue, but their cellular impact is unclear. This study maps the cycling human breast, revealing how obesity and pregnancy alter hormone responses in breast cells.
Area of Science:
- Reproductive biology
- Endocrinology
- Genomics
Background:
- Estrogen and progesterone fluctuations influence breast development and cancer risk.
- Hormonal effects on individual breast cell types are poorly understood due to indirect paracrine signaling.
- A comprehensive map of the cycling human breast is needed.
Purpose of the Study:
- To reveal the network of transcriptional programs in the human breast responding to hormonal changes.
- To understand how cell-cell interactions and individual variability contribute to hormone response.
- To investigate the distinct mechanisms by which pregnancy and obesity modify breast cell hormone responsiveness.
Main Methods:
- Single-cell RNA sequencing of premenopausal breast tissue.
- Development of a computational approach (DECIPHER-seq) to analyze cell-type proportions and transcriptional programs.
- Leveraging inter-individual variability in breast composition and cell states.
Main Results:
- Identified coordinated transcriptional programs representing the tissue-level response to hormone level changes.
- Inferred hormone-regulated cell-cell interactions based on cell-type proportion variations.
- Demonstrated that obesity reduces hormone-responsive cell proportions, while pregnancy dampens direct cellular hormone response.
Conclusions:
- Provided a comprehensive map of the cycling human breast's response to hormones.
- Elucidated distinct roles of obesity and pregnancy in modulating breast cell hormone sensitivity.
- Established a framework for understanding paracrine networks in hormonal regulation of breast tissue.
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