AP-2γ Is Required for Maintenance of Multipotent Mammary Stem Cells

Mammary gland ductal morphogenesis depends on the differentiation of mammary stem cells (MaSCs) into basal and luminal lineages. The AP-2 gamma transcription factor, encoded by Tfap2c, has a central role in mammary gland development but its effect in mammary lineages and specifically MaSCs is largely unknown. Here, we utilized an inducible, conditional knockout of Tfap2c to elucidate the role of AP-2 gamma in maintenance and differentiation of MaSCs. Loss of AP-2 gamma in the basal epithelium profoundly altered the transcriptomes and decreased the number of cells within several clusters of mammary epithelial cells, including adult MaSCs and luminal progenitors. AP-2 gamma regulated the expression of genes known to be required for mammary development, including Cebpb, Nfkbia, and Rspo1. As a result, AP-2 gamma-deficient mice exhibited repressed mammary gland ductal outgrowth and inhibition of regenerative capacity. The findings demonstrate that AP-2 gamma can regulate development of mammary gland structures potentially regulating maintenance and differentiation of multipotent MaSCs.

Automated summary

The AP-2 gamma transcription factor plays a crucial role in the maintenance and differentiation of mammary stem cells, with loss of AP-2 gamma leading to altered mammary gland structures and inhibited regenerative capacity.