TCF/Lef1 activity controls establishment of diverse stem and progenitor cell compartments in mouse epidermis
Open Access
- 21 June 2011
- journal article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 30 (15), 3004-3018
- https://doi.org/10.1038/emboj.2011.199
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.This publication has 69 references indexed in Scilit:
- Polarization of Tumor-Associated Macrophages: A Novel Strategy for Vascular Normalization and Antitumor ImmunityCancer Cell, 2011
- Basal Cell Carcinomas Arise from Hair Follicle Stem Cells in Ptch1+/− MiceCancer Cell, 2011
- Dynamics between Stem Cells, Niche, and Progeny in the Hair FollicleCell, 2011
- The Ordered Architecture of Murine Ear Epidermis Is Maintained by Progenitor Cells with Random FateDevelopmental Cell, 2010
- Distinct Self-Renewal and Differentiation Phases in the Niche of Infrequently Dividing Hair Follicle Stem CellsCell Stem Cell, 2009
- Lrig1 Expression Defines a Distinct Multipotent Stem Cell Population in Mammalian EpidermisCell Stem Cell, 2009
- A Two-Step Mechanism for Stem Cell Activation during Hair RegenerationCell Stem Cell, 2009
- Hair Follicle Stem Cells Are Specified and Function in Early Skin MorphogenesisCell Stem Cell, 2008
- NFATc1 Balances Quiescence and Proliferation of Skin Stem CellsCell, 2008
- Blimp1 Defines a Progenitor Population that Governs Cellular Input to the Sebaceous GlandCell, 2006