title: StromalGli2activity coordinates a niche signaling program for mammary epithelial stem cells.
abstract: The stem cell niche is a complex local signaling microenvironment that sustains stem cell activity during organ maintenance and regeneration. The mammary gland niche must support its associated stem cells while also responding to systemic hormonal regulation that triggers pubertal changes. We find thatGli2, the major Hedgehog pathway transcriptional effector, acts within mouse mammary stromal cells to direct a hormone-responsive niche signaling program by activating expression of factors that regulate epithelial stem cells as well as receptors for the mammatrophic hormones estrogen and growth hormone. Whereas prior studies implicate stem cell defects in human disease, this work shows that niche dysfunction may also cause disease, with possible relevance for human disorders and in particular the breast growth pathogenesis associated with combined pituitary hormone deficiency.
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.|Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Chen
authors.identifier: 0000-0003-4501-5591
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Shang
authors.identifier: 0000-0003-0630-7719
authors.initials: S
authors.lastname: Cai
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.|Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.|Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyumgbuk 37673, South Korea.
authors.forename: Kunyoo
authors.initials: K
authors.lastname: Shin
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.|Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Agnes
authors.identifier: 0000-0002-6618-2500
authors.initials: A
authors.lastname: Lim
authors.affiliation: Faculty of Engineering and Institute for Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat Gan 52900, Israel.
authors.forename: Tomer
authors.initials: T
authors.lastname: Kalisky
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.|Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Wan-Jin
authors.identifier: 0000-0002-2186-9800
authors.initials: WJ
authors.lastname: Lu
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Clarke
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. pbeachy@stanford.edu.|Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.|Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.|Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Philip A
authors.identifier: 0000-0003-1098-9046
authors.initials: PA
authors.lastname: Beachy
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D004967:Estrogens / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D013006:Growth Hormone / Q000097:blood / Q000172:deficiency / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D008321:Mammary Glands, Animal / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D011388:Prolactin / Q000378:metabolism; D012741:Sexual Maturation / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D055153:Stem Cell Niche / Q000235:genetics*; D017154:Stromal Cells / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics; D000075746:Zinc Finger Protein Gli2 / Q000235:genetics / Q000502:physiology*
chemical_list: D004967:Estrogens; C000618551:Gli2 protein, mouse; D053823:Hedgehog Proteins; C513121:IGF2 protein, mouse; C561116:WNT2A protein, mouse; D051153:Wnt Proteins; D000075746:Zinc Finger Protein Gli2; D007335:Insulin-Like Growth Factor II; D011388:Prolactin; D013006:Growth Hormone