@article{a3a941caddce4db8bd19aa90dbff626d,
title = "miR-205 Regulates Basal Cell Identity and Stem Cell Regenerative Potential During Mammary Reconstitution",
abstract = "Mammary gland development is fueled by stem cell self-renewal and differentiation. External cues from the microenvironment coupled with internal cues such as post-transcriptional regulation exerted by microRNAs regulate stem cell behavior and fate. Here, we have identified a miR-205 regulatory network required for mammary gland ductal development and stem cell regeneration following transplantation into the cleared mammary fat pad. In the postnatal mammary gland, miR-205 is predominantly expressed in the basal/stem cell enriched population. Conditional deletion of miR-205 in mammary epithelial cells impairs stem cell self-renewal and mammary regenerative potential in the in vitro mammosphere formation assay and in vivo mammary reconstitution. miR-205 null transplants display significant changes in basal cells, basement membrane, and stroma. NKD1 and PTPA, which inhibit the Wnt signaling pathway, and AMOT, which causes YAP cytoplasmic retention and inactivation were identified as miR-205 downstream mediators. These studies also confirmed that miR-205 is a direct ΔNp63 target gene that is critical for the regulation of basal cell identity. Stem Cells 2018;36:1875–15.",
keywords = "Mammary gland ductal development, Stem cell regenerative potential, Wnt, YAP, miR-205",
author = "Yang Lu and Jin Cao and Marco Napoli and Zheng Xia and Na Zhao and Creighton, {Chad J.} and Wei Li and Xi Chen and Flores, {Elsa R.} and McManus, {Michael T.} and Rosen, {Jeffrey M.}",
note = "Funding Information: This project was supported by the Genomics and RNA Profiling Core, the Integrated Microscopy Core with funding from NIH (HD007495, DK56338, and CA125123), the Lester and Sue Smith Breast Center Pathology Core and the Cytometry and Cell Sorting Core with funding from NIH (AI036211, CA125123, and RR024574) and the expert assistance of Joel M. Sederstrom at Baylor College of Medicine. The authors would like to thank Drs. Li Ma and Sue-Hwa Lin from MD Anderson Cancer Center for providing YAP, pYAP, and AMOT antibodies, respectively. The authors would also like to thank Drs. Kevin Roarty, Deanna Acosta, Se-Jin Kim, Chi-Hsuan Chang, and Amulya Sreekumar for critical reading and editing of the manuscript. This work was supported by grants NCI R35CA197452 to E. R. Flores, 4R01CA016303-41 to J.M. Rosen, and 1U19CA179513-01 and 1R01OD019128-01 to M.T. McManus. Funding Information: This project was supported by grants NCI R35CA197452, 4R01CA016303-41, 1U19CA179513-01, and 1R01OD019128-01, and the Genomics and RNA Profiling Core, the Integrated Microscopy Core, the Lester and Sue Smith Breast Center Pathology Core, and the Cytometry and Cell Sorting Core. Publisher Copyright: {\textcopyright} AlphaMed Press 2018",
year = "2018",
month = dec,
doi = "10.1002/stem.2914",
language = "English (US)",
volume = "36",
pages = "1875--1889",
journal = "Stem Cells",
issn = "1066-5099",
publisher = "AlphaMed Press",
number = "12",
}