Journal article
AP-2γ Is Required for Maintenance of Multipotent Mammary Stem Cells
Stem cell reports, Vol.16(1), pp.106-119
01/12/2021
DOI: 10.1016/j.stemcr.2020.12.002
PMCID: PMC7897584
PMID: 33382976
Abstract
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.
•AP-2γ-deficient mice exhibit repressed ductal outgrowth and regenerative capacity•Loss of AP-2γ reduced cells within mammary stem and luminal progenitor clusters•AP-2γ target genes, including Cebpb, Nfkbia, and Rspo1, regulate mammary development•AP-2γ potentially regulates maintenance of multipotent mammary stem cells
Gu and colleagues utilized a conditional knockout of Tfap2c to examine transcriptional effects of AP-2γ on mammary development. AP-2γ-deficient mice have decreased numbers of cell populations harboring mammary stem cells and have altered expression of genes required for mammary development, including Cebpb, Nfkbia, and Rspo1. They demonstrate that AP-2γ is implicated in maintenance of multipotent mammary stem cells.
Details
- Title: Subtitle
- AP-2γ Is Required for Maintenance of Multipotent Mammary Stem Cells
- Creators
- Vivian W. Gu - University of IowaEdward Cho - University of IowaDakota T. Thompson - University of IowaVictoria C. Cassady - University of IowaNicholas Borcherding - University of IowaKelsey E. Koch - University of IowaVincent T. Wu - University of IowaAllison W. Lorenzen - University of IowaDana M. van der Heide - University of IowaJeffrey R. White - University of IowaMikhail V. Kulak - University of IowaTrevor Williams - University of Colorado Anschutz Medical CampusWeizhou Zhang - University of FloridaRonald J. Weigel - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Stem cell reports, Vol.16(1), pp.106-119
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.stemcr.2020.12.002
- PMID
- 33382976
- PMCID
- PMC7897584
- ISSN
- 2213-6711
- eISSN
- 2213-6711
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health
- Language
- English
- Date published
- 01/12/2021
- Academic Unit
- Dermatology; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Surgery; Radiation Oncology; Biochemistry and Molecular Biology
- Record Identifier
- 9984284344602771
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