Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 119, Issue 15, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2121720119
Keywords
single-cell RNA-sequencing; breast milk; mammary epithelial cell; macrophage; maternal health
Categories
Funding
- NIH [R01HG010959]
- National Research Service Award postdoctoral Fellowship [F32-AI136459]
- Beckman Young Investigator Program
- Sloan Fellowship in Chemistry
- Massachusetts Institute of Technology (Charles E. Reed Faculty Initiative)
- National Science Foundation Graduate Research Fellowship [1122374]
- Koch Institute Support (core) NIH Grant [P30-CA14051]
- Massachusetts Institute of Technology-Glaxo SmithKline Gertrude B. Elion postdoctoral fellowship
- Columbia University Office of the Provost grants
- Weizmann Institute of Science National Postdoctoral Award Program for Advancing Women in Science
- International Society for Research In Human Milk and Lactation Trainee Bridge Fund
- Human Frontier Science Program
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This study utilized single-cell RNA sequencing technology to investigate the cellular composition of human breast milk. The findings revealed different subtypes of lactocytes and macrophages, as well as their changes during lactation. This research provides important insights into the lactational process and has implications for supporting healthy lactation and milk production.
Human breast milk (hBM) is a dynamic fluid that contains millions of cells, but their identities and phenotypic properties are poorly understood. We generated and analyzed single-cell RNA-sequencing (scRNA-seq) data to characterize the transcriptomes of cells from hBM across lactational time from 3 to 632 d postpartum in 15 donors. We found that the majority of cells in hBM are lactocytes, a specialized epithelial subset, and that cell-type frequencies shift over the course of lactation, yielding greater epithelial diversity at later points. Analysis of lactocytes reveals a continuum of cell states characterized by transcriptional changes in hormone-, growth factor-, and milk production-related pathways. Generalized additive models suggest that one subcluster, LC1 epithelial cells, increases as a function of time postpartum, daycare attendance, and the use of hormonal birth control. We identify several subclusters of macrophages in hBM that are enriched for tolerogenic functions, possibly playing a role in protecting the mammary gland during lactation. Our description of the cellular components of breast milk, their association with maternal-infant dyad metadata, and our quantification of alterations at the gene and pathway levels provide a detailed longitudinal picture of hBM cells across lactational time. This work paves the way for future investigations of how a potential division of cellular labor and differential hormone regulation might be leveraged therapeutically to support healthy lactation and potentially aid in milk production.
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