Transcriptional changes in the mammary gland during lactation revealed by single cell sequencing of cells from human milk

• Published in: Nature communications Vol. 13; no. 1; p. 562
• Main Authors: Twigger, Alecia-Jane, Engelbrecht, Lisa K., Bach, Karsten, Schultz-Pernice, Isabel, Pensa, Sara, Stenning, Jack, Petricca, Stefania, Scheel, Christina H., Khaled, Walid T.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.01.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 13/31; 38/91; 631/1647/514/1949; 631/443/494; 631/61/514/1949; 631/80/86; 692/699/67/1347; Breast - cytology; Breast - metabolism; Breast cancer; Breast milk; Breastfeeding & lactation; Cell Culture Techniques, Three Dimensional - methods; Cells, Cultured; Cluster Analysis; Epithelial cells; Epithelium; Female; Gene Expression Profiling - methods; Gene Regulatory Networks; Hormones; Humanities and Social Sciences; Humans; Immune system; Immune System - cytology; Immune System - metabolism; Lactation; Lactation - genetics; Mammary gland; Mammary glands; Mammary Glands, Human - cytology; Mammary Glands, Human - metabolism; Milk; Milk, Human - cytology; Milk, Human - metabolism; multidisciplinary; Offspring; Pregnancy; Progenitor cells; Science; Science (multidisciplinary); Single-Cell Analysis - methods; Stem cells; Stromal Cells - cytology; Stromal Cells - metabolism; Tissues; Transcription; Transcriptomics
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-27895-0

Under normal conditions, the most significant expansion and differentiation of the adult mammary gland occurs in response to systemic reproductive hormones during pregnancy and lactation to enable milk synthesis and secretion to sustain the offspring. However, human mammary tissue remodelling that takes place during pregnancy and lactation remains poorly understood due to the challenge of acquiring samples. We report here single-cell transcriptomic analysis of 110,744 viable breast cells isolated from human milk or non-lactating breast tissue, isolated from nine and seven donors, respectively. We found that human milk largely contains epithelial cells belonging to the luminal lineage and a repertoire of immune cells. Further transcriptomic analysis of the milk cells identified two distinct secretory cell types that shared similarities with luminal progenitors, but no populations comparable to hormone-responsive cells. Taken together, our data offers a reference map and a window into the cellular dynamics that occur during human lactation and may provide further insights on the interplay between pregnancy, lactation and breast cancer. Human mammary tissue remodelling that takes place during pregnancy and lactation remains poorly understood. Here the authors characterize cells in human milk, identifying epithelial cells resembling luminal progenitors and immune cells, contributing insights into this process.