Department of Surgery, University of Iowa, 200 Hawkins Drive, JCP 1509 Iowa City, IA 52242-1086, USA; Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA.
Department of Surgery, University of Iowa, 200 Hawkins Drive, JCP 1509 Iowa City, IA 52242-1086, USA.
Stem Cell Reports. 2021 Jan 12;16(1):106-119. doi: 10.1016/j.stemcr.2020.12.002. Epub 2020 Dec 30.
Mammary gland ductal morphogenesis depends on the differentiation of mammary stem cells (MaSCs) into basal and luminal lineages. The AP-2γ 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-2γ in maintenance and differentiation of MaSCs. Loss of AP-2γ 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-2γ regulated the expression of genes known to be required for mammary development, including Cebpb, Nfkbia, and Rspo1. As a result, AP-2γ-deficient mice exhibited repressed mammary gland ductal outgrowth and inhibition of regenerative capacity. The findings demonstrate that AP-2γ can regulate development of mammary gland structures potentially regulating maintenance and differentiation of multipotent MaSCs.
乳腺导管形态发生依赖于乳腺干细胞（MaSCs）向基底和腔谱系的分化。由 Tfap2c 编码的 AP-2γ 转录因子在乳腺发育中具有核心作用，但它在乳腺谱系中，特别是 MaSCs 中的作用在很大程度上尚不清楚。在这里，我们利用诱导型、条件性 Tfap2c 敲除来阐明 AP-2γ 在 MaSCs 维持和分化中的作用。AP-2γ 在基底上皮中的缺失显著改变了转录组，并减少了几个乳腺上皮细胞簇中的细胞数量，包括成年 MaSCs 和腔祖细胞。AP-2γ 调节了已知对乳腺发育至关重要的基因的表达，包括 Cebpb、Nfkbia 和 Rspo1。因此，AP-2γ 缺陷小鼠表现出乳腺导管生长受抑制和再生能力受抑制。这些发现表明，AP-2γ 可以调节乳腺结构的发育，可能调节多能 MaSCs 的维持和分化。
