Cellular and transcriptional diversity over the course of human lactation

Biology Biology
Cell Atlas Cell Atlas
Genomics Genomics
Immunology Immunology
Medicine Medicine
Alex K. Shalek Alex K. Shalek
Ben Mead Ben Mead
Brittany Goods Brittany Goods
Kellie Kolb Kellie Kolb
Patricia Gao Patricia Gao
Riley Drake Riley Drake
Sarah Nyquist Sarah Nyquist

Nyquist et al.▾ Nyquist, S.K., Gao, P., Haining, T.K.J., Retchin, M.R., Golan, Y., Drake, R.S., Kolb, K., Mead, B.E., Ahituv, N., Martinez, M.E., Shalek, A.K.*, Berger, B., Goods, B.A.

PNAS , Volume 119

April, 2022


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.