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

Aleksandra Piwko-Czuchra; Heidi Koegel; Hannelore Meyer; Martina Bauer; Sabine Werner; Cord Brakebusch; Reinhard Fässler

doi:10.1371/journal.pone.0005488

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

Aleksandra Piwko-Czuchra, Heidi Koegel, Hannelore Meyer, Martina Bauer, Sabine Werner, Cord Brakebusch, Reinhard Fässler

Biomedicinsk Institut

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

43 Citationer (Scopus)

Abstract

Udgivelsesdato: 2009-null

Originalsprog	Engelsk
Tidsskrift	PLoS ONE
Vol/bind	4
Udgave nummer	5
Sider (fra-til)	e5488
ISSN	1932-6203
DOI	https://doi.org/10.1371/journal.pone.0005488
Status	Udgivet - 2009

Bibliografisk note

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

Adgang til dokumentet

10.1371/journal.pone.0005488

Citationsformater

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title = "Beta1 integrin-mediated adhesion signalling is essential for epidermal progenitor cell expansion",

abstract = "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.",

author = "Aleksandra Piwko-Czuchra and Heidi Koegel and Hannelore Meyer and Martina Bauer and Sabine Werner and Cord Brakebusch and Reinhard F{\"a}ssler",

note = "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",

year = "2009",

doi = "10.1371/journal.pone.0005488",

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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

SN - 1932-6203

VL - 4

SP - e5488

JO - PLoS ONE

JF - PLoS ONE

IS - 5

ER -