AP-2γ is Required for Maintenance of Pluripotent Mammary Stem Cells

Gu, V. W.; Cho, E.; Thompson, D. T.; Cassady, V. C.; Borcherding, N.; Koch, K. E.; Wu, V. T.; Lorenzen, A. W.; Kulak, M. V.; Williams, T.; Zhang, W.; Weigel, R. J.

doi:10.1101/2020.06.10.107078

bioRxiv · 10.1101/2020.06.10.107078

AP-2γ is Required for Maintenance of Pluripotent Mammary Stem Cells

Gu, V. W.·Cho, E.·Thompson, D. T.·Cassady, V. C.·Borcherding, N.·Koch, K. E.·Wu, V. T.·Lorenzen, A. W.·Kulak, M. V.·Williams, T.·Zhang, W.·Weigel, R. J.

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Abstract

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. Herein, 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 C/EBP{beta}, I{kappa}B, 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} is required for maintenance of pluripotent MaSCs and their ability to develop mammary gland structures. HighlightsO_LIAP-2{gamma}-deficient mice exhibited repressed ductal outgrowth and regenerative capacity C_LIO_LILoss of AP-2{gamma} reduced the number of mammary stem and luminal progenitor cells C_LIO_LIAP-2{gamma} target genes, including C/EBP{beta}, I{kappa}B, and Rspo1, regulate mammary development C_LIO_LIAP-2{gamma} is required for maintenance of pluripotent mammary stem cells C_LI eTOC blurbGu, Cho and colleagues utilized a conditional knockout of Tfap2c to examine transcriptional effects of AP-2{gamma} on mammary stem cells. Single cell analysis demonstrated that AP-2{gamma}-deficient mice have decreased numbers of mammary stem cells and alteration of genes required for mammary development including C/EBP{beta}, I{kappa}B, and Rspo1. They demonstrate that AP-2{gamma} is necessary for maintenance of pluripotent mammary stem cells.

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Gu, V. W., Cho, E., Thompson, D. T., Cassady, V. C., Borcherding, N., Koch, K. E., Wu, V. T., Lorenzen, A. W., Kulak, M. V., Williams, T., Zhang, W., Weigel, R. J.. 2020-06-10. AP-2γ is Required for Maintenance of Pluripotent Mammary Stem Cells. https://doi.org/10.1101/2020.06.10.107078

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