naa a22 4500 528783424 20180924065515.0 cr unu---uuuuu 180924e20090508xx s 000 0 eng 10.3929/ethz-b-000015785 doi 10.1371/journal.pone.0005488 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/15785 β1 integrin-mediated adhesion signalling is essential for epidermal progenitor cell expansion [Elektronische Daten] [Aleksandra Piwko-Czuchra, Heidi Koegel, Hannelore Meyer, Martina Bauer, Sabine Werner, Cord Brakebusch, Reinhard Fässler] PLoS ONE Open access ethresearch Background There is a major discrepancy between the in vitro and in vivo results regarding the role of β1 integrins in the maintenance of epidermal stem/progenitor cells. Studies of mice with skin-specific ablation of β1 integrins suggested that epidermis can form and be maintained in their absence, while in vitro data have shown a fundamental role for these adhesion receptors in stem/progenitor cell expansion and differentiation. Methodology/Principal Findings To elucidate this discrepancy we generated hypomorphic mice expressing reduced β1 integrin levels on keratinocytes that developed similar, but less severe defects than mice with β1-deficient keratinocytes. Surprisingly we found that upon aging these abnormalities attenuated due to a rapid expansion of cells, which escaped or compensated for the down-regulation of β1 integrin expression. A similar phenomenon was observed in aged mice with a complete, skin-specific ablation of the β1 integrin gene, where cells that escaped Cre-mediated recombination repopulated the mutant skin in a very short time period. The expansion of β1 integrin expressing keratinocytes was even further accelerated in situations of increased keratinocyte proliferation such as wound healing. Conclusions/Significance These data demonstrate that expression of β1 integrins is critically important for the expansion of epidermal progenitor cells to maintain epidermal homeostasis. Creative Commons Attribution 3.0 Unported http://creativecommons.org/licenses/by/3.0 ethresearch Piwko-Czuchra Aleksandra joint author Koegel Heidi joint author Meyer Hannelore joint author Bauer Martina joint author Werner Sabine joint author Brakebusch Cord joint author Fässler Reinhard joint author PLoS ONE San Francisco, CA : Public Library of Science 4 (5), p. e5488 1932-6203 http://hdl.handle.net/20.500.11850/15785 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/15785 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 700 1- Piwko-Czuchra Aleksandra joint author ETHRESEARCH 700 1- Koegel Heidi joint author ETHRESEARCH 700 1- Meyer Hannelore joint author ETHRESEARCH 700 1- Bauer Martina joint author ETHRESEARCH 700 1- Werner Sabine joint author ETHRESEARCH 700 1- Brakebusch Cord joint author ETHRESEARCH 700 1- Fässler Reinhard joint author ETHRESEARCH 773 0- PLoS ONE San Francisco, CA : Public Library of Science 4 (5), p. e5488 1932-6203 BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access