title: TCF/Lef1 activity controls establishment of diverse stem and progenitor cell compartments in mouse epidermis.
abstract: Mammalian epidermis consists of the interfollicular epidermis, hair follicles (HFs) and associated sebaceous glands (SGs). It is constantly renewed by stem and progenitor cell populations that have been identified and each compartment features a distinct mechanism of cellular turnover during renewal. The functional relationship between the diverse stem cell (SC) pools is not known and molecular signals regulating the establishment and maintenance of SC compartments are not well understood. Here, we performed lineage tracing experiments to demonstrate that progeny of HF bulge SCs transit through other SC compartments, suggesting a hierarchy of competent multipotent keratinocytes contributing to tissue renewal. The bulge was identified as a bipotent SC compartment that drives both cyclic regeneration of HFs and continuous renewal of SGs. Our data demonstrate that aberrant signalling by TCF/Lef1, transcription factors crucial for bulge SC activation and hair differentiation, results in development of ectopic SGs originating from bulge cells. This process of de novo SG formation is accompanied by the establishment of new progenitor niches. Detailed molecular analysis suggests the recapitulation of steps of tissue morphogenesis.
authors.affiliation: Center for Molecular Medicine Cologne (CMMC), Institute of Pathology, University of Cologne, Cologne, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Petersson
authors.forename: Heike
authors.initials: H
authors.lastname: Brylka
authors.forename: Andreas
authors.initials: A
authors.lastname: Kraus
authors.forename: Susan
authors.initials: S
authors.lastname: John
authors.forename: Gunter
authors.initials: G
authors.lastname: Rappl
authors.forename: Peter
authors.initials: P
authors.lastname: Schettina
authors.forename: Catherin
authors.initials: C
authors.lastname: Niemann
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D015870:Gene Expression; D018859:Hair Follicle / Q000166:cytology*; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis; D012627:Sebaceous Glands / Q000166:cytology; D013234:Stem Cells / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D043562:Receptors, G-Protein-Coupled; C497574:Lef1 protein, mouse; C548022:Lgr6 protein, mouse; C101671:Lrig1 protein, mouse; C075668:Tcf3 protein, mouse