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Distinct lactation-associated macrophages exist in murine mammary tissue and human milk [RNA-seq: mouse]

ABSTRACT: Macrophages are involved in immune defense, organogenesis and tissue homeostasis. They also contribute to the different phases of mammary gland remodeling during development, pregnancy and involution post-lactation. Yet, less is known about the dynamics of mammary gland macrophages in the lactation stage. Here, we describe a macrophage population present during lactation in mice. By multi-parameter flow cytometry and single-cell RNA sequencing we reveal this population as distinct from the two resident macrophage subsets present pregestationally. These lactation-induced macrophages (LiMacs) are predominantly monocyte-derived and expand by proliferation in situ concomitant with nursing. LiMacs develop independently of IL-34 but require CSF-1 signaling and are partly microbiota-dependent. Locally, they reside adjacent to the basal cells of the alveoli and extravasate into the milk. Moreover, we also found several macrophage subsets in human milk, resembling LiMacs. Collectively, these findings reveal the emergence of unique macrophages in the mammary gland and milk during lactation.

ORGANISM(S): Mus musculus

PROVIDER: GSE230697 | GEO | 2023/05/03

REPOSITORIES: GEO

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Project description:Non-steroidal anti-inflammatory drug activated gene 1 (NAG-1) plays some role in reducing obesity in mice overexpressing human NAG-1, even on a high fat diet. Male and female hNAG-1 expressing mice have reduced body weight, increased longevity and metabolic activity. This study investigates the role of hNAG-1 in female reproduction and finds that the female mice have reduced fertility and pup survival after birth. Examination of the mammary glands in these mice suggests that hNAG-1 overexpressing mice have altered mammary epithelial development during pregnancy, including reduced occupancy of the fat pad and increased apoptosis via TUNEL positive cells at lactation day 2. Pups nursing from hNAG-1 overexpressing dams have reduced milk spots compared to pups nursing from WT dams. When CD-1 pups were cross-fostered with hNAG-1 or WT dams; reduced milk volume was observed in pups nursing from hNAG-1 dams compared to pups nursing from WT dams in a lactation challenge study. Milk was isolated from WT and hNAG-1 dams, and the milk was found to have secreted NAG-1 protein (approximately 25ng/mL) from hNAG-1 dams compared to WT dams, which had no detectable NAG-1 in the milk. A decrease in non-esterified free fatty acids in the milk of hNAG-1 dams was observed. Altered milk composition suggests that the pups were receiving inadequate nutrients during perinatal development; to examine this hypothesis serum was isolated from pups and clinical chemistry points were measured. Male and female pups nursing from hNAG-1 dams had reduced serum triglyceride concentrations. Cidea/CIDEA expression was reduced in hNAG-1 mammary glands, and microarray analysis suggests that genes involved in lipid metabolism are differentially expressed in hNAG-1 mammary glands. This study suggests that overexpression of hNAG-1 impairs lactational differentiation and pup survival due to altered milk quality and quantity 4 WT mammary glands on lactation day 2 and 5 hNAG-1 transgenic mice mammary glands on lactation day 2 were used.

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Distinct lactation-associated macrophages exist in murine mammary tissue and human milk [RNA-seq: mouse]

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