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C/EBPβ deletion in macrophages impairs alveolar budding by altering the Wnt landscape during mammary gland development

ABSTRACT: Macrophages have important roles in mammary gland development and tissue homeostasis, but the specific mechanisms that regulate macrophage function need further elucidation. We have identified C/EBPβ as an important macrophage factor that is present in multiple populations of the normal mammary gland. Mammary glands from mice with C/EBPβ-deficient macrophages showed a significant decrease in alveolar budding during the estrus cycle. Deletion of C/EBPβ from macrophages resulted in changes in cytokine production, and an inability of both epithelial cells and macrophages to respond progesterone. RNA sequencing showed significant changes in PR-responsive genes and alterations in the Wnt landscape of epithelial cells in mammary glands that lacked C/EBPbeta in macrophages, which have been shown to mediate stem cell expansion during diestrus. These studies suggest that C/EBPbeta is a critical macrophage factor that facilitates macrophage-epithelial crosstalk during a key stage of mammary gland tissue homeostasis, and have critical implications for how disruption of tissue homeostasis can lead to tumorigenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE225295 | GEO | 2024/07/16

REPOSITORIES: GEO

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