title: Compartmentalized Epidermal Activation of β-Catenin Differentially Affects Lineage Reprogramming and Underlies Tumor Heterogeneity.
abstract: Wnt/β-catenin activation in adult epidermis can induce new hair follicle formation and tumor development. We used lineage tracing to uncover the relative contribution of different stem cell populations. LGR6(+) and LRIG1(+) stem cells contributed to ectopic hair follicles formed in the sebaceous gland upon β-catenin activation, whereas LGR5(+) cells did not. Lgr6, but not Lrig1 or Lgr5, was expressed in a subpopulation of interfollicular epidermal cells that were competent to form new hair follicles. Oncogenic β-catenin expression in LGR5(+) cells led to formation of pilomatricomas, while LRIG1(+) cells formed trichoadenomas and LGR6(+) cells formed dermatofibromas. Tumor formation was always accompanied by a local increase in dermal fibroblast density and transient extracellular matrix remodeling. However, each tumor had a distinct stromal signature in terms of immune cell infiltrate and expression of CD26 and CD44. We conclude that compartmentalization of epidermal stem cells underlies different responses to β-catenin and skin tumor heterogeneity.
authors.affiliation: Centre for Stem Cells and Regenerative Medicine, King's College London, 28(th) Floor, Tower Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK; Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
authors.forename: Kai
authors.initials: K
authors.lastname: Kretzschmar
authors.affiliation: Centre for Stem Cells and Regenerative Medicine, King's College London, 28(th) Floor, Tower Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK; Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
authors.forename: Christine
authors.initials: C
authors.lastname: Weber
authors.affiliation: Centre for Stem Cells and Regenerative Medicine, King's College London, 28(th) Floor, Tower Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
authors.forename: Ryan R
authors.initials: RR
authors.lastname: Driskell
authors.affiliation: Dermatopathology Laboratory, St. John's Institute of Dermatology, St. Thomas' Hospital, Westminster Bridge Road, London SE1 7EH, UK.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Calonje
authors.affiliation: Centre for Stem Cells and Regenerative Medicine, King's College London, 28(th) Floor, Tower Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK. Electronic address: fiona.watt@kcl.ac.uk.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Watt
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D051379:Mice; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051176:beta Catenin