AP-2γ is Required for Maintenance of Pluripotent Mammary Stem Cells
AP-2γ is Required for Maintenance of Pluripotent Mammary Stem Cells
SUMMARY 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. Herein, 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 C/EBPβ, IκBα, 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 is required for maintenance of pluripotent MaSCs and their ability to develop mammary gland structures. HighlightsAP-2γ-deficient mice exhibited repressed ductal outgrowth and regenerative capacityLoss of AP-2γ reduced the number of mammary stem and luminal progenitor cellsAP-2γ target genes, including C/EBPβ, IκBα, and Rspo1, regulate mammary developmentAP-2γ is required for maintenance of pluripotent mammary stem cells eTOC blurbGu, Cho and colleagues utilized a conditional knockout of Tfap2c to examine transcriptional effects of AP-2γ on mammary stem cells. Single cell analysis demonstrated that AP-2γ-deficient mice have decreased numbers of mammary stem cells and alteration of genes required for mammary development including C/EBPβ, IκBα, and Rspo1. They demonstrate that AP-2γ is necessary for maintenance of pluripotent mammary stem cells.
Gu Vivian W.、Cho Edward、Borcherding Nicholas、Koch Kelsey E.、Kulak Mikhail V.、Weigel Ronald J.、Zhang Weizhou、Thompson Dakota T.、Lorenzen Allison W.、Wu Vincent T.、Williams Trevor、Cassady Victoria C.
Department of Surgery, University of Iowa||Department of Molecular Physiology and Biophysics, University of IowaDepartment of Surgery, University of IowaDepartment of Pathology, University of IowaDepartment of Surgery, University of IowaDepartment of Surgery, University of IowaDepartment of Surgery, University of Iowa||Department of Molecular Physiology and Biophysics, University of Iowa||Department of Biochemistry, University of IowaDepartment of Pathology, Immunology, and Laboratory Medicine, University of FloridaDepartment of Surgery, University of IowaDepartment of Surgery, University of IowaDepartment of Surgery, University of IowaDepartment of Craniofacial Biology, University of Colorado Anschutz Medical CampusDepartment of Surgery, University of Iowa
分子生物学细胞生物学遗传学
Mammary GlandDevelopmentTFAP2CAP-2γ
Gu Vivian W.,Cho Edward,Borcherding Nicholas,Koch Kelsey E.,Kulak Mikhail V.,Weigel Ronald J.,Zhang Weizhou,Thompson Dakota T.,Lorenzen Allison W.,Wu Vincent T.,Williams Trevor,Cassady Victoria C..AP-2γ is Required for Maintenance of Pluripotent Mammary Stem Cells[EB/OL].(2025-03-28)[2025-04-26].https://www.biorxiv.org/content/10.1101/2020.06.10.107078.点此复制
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