TY - JOUR

T1 - Beta1 integrin-mediated adhesion signalling is essential for epidermal progenitor cell expansion

AU - Piwko-Czuchra, Aleksandra

AU - Koegel, Heidi

AU - Meyer, Hannelore

AU - Bauer, Martina

AU - Werner, Sabine

AU - Brakebusch, Cord

AU - Fässler, Reinhard

N1 - Keywords: Aging; Alleles; Animals; Antigens, CD29; Cell Adhesion; Cell Count; Cell Proliferation; Codon, Nonsense; Crosses, Genetic; Epidermis; Female; Gene Deletion; Genotype; Heterozygote; Integrases; Keratin-5; Keratinocytes; Male; Mice; Phenotype; Recombination, Genetic; Signal Transduction; Skin; Stem Cells

PY - 2009

Y1 - 2009

N2 - BACKGROUND: There is a major discrepancy between the in vitro and in vivo results regarding the role of beta1 integrins in the maintenance of epidermal stem/progenitor cells. Studies of mice with skin-specific ablation of beta1 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 beta1 integrin levels on keratinocytes that developed similar, but less severe defects than mice with beta1-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 beta1 integrin expression. A similar phenomenon was observed in aged mice with a complete, skin-specific ablation of the beta1 integrin gene, where cells that escaped Cre-mediated recombination repopulated the mutant skin in a very short time period. The expansion of beta1 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 beta1 integrins is critically important for the expansion of epidermal progenitor cells to maintain epidermal homeostasis.

AB - BACKGROUND: There is a major discrepancy between the in vitro and in vivo results regarding the role of beta1 integrins in the maintenance of epidermal stem/progenitor cells. Studies of mice with skin-specific ablation of beta1 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 beta1 integrin levels on keratinocytes that developed similar, but less severe defects than mice with beta1-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 beta1 integrin expression. A similar phenomenon was observed in aged mice with a complete, skin-specific ablation of the beta1 integrin gene, where cells that escaped Cre-mediated recombination repopulated the mutant skin in a very short time period. The expansion of beta1 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 beta1 integrins is critically important for the expansion of epidermal progenitor cells to maintain epidermal homeostasis.

U2 - 10.1371/journal.pone.0005488

DO - 10.1371/journal.pone.0005488

M3 - Journal article

C2 - 19424505

VL - 4

SP - e5488

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 5

ER -