Dataset Information

Skin fibrosis. Identification and isolation of a dermal lineage with intrinsic fibrogenic potential.

ABSTRACT: Dermal fibroblasts represent a heterogeneous population of cells with diverse features that remain largely undefined. We reveal the presence of at least two fibroblast lineages in murine dorsal skin. Lineage tracing and transplantation assays demonstrate that a single fibroblast lineage is responsible for the bulk of connective tissue deposition during embryonic development, cutaneous wound healing, radiation fibrosis, and cancer stroma formation. Lineage-specific cell ablation leads to diminished connective tissue deposition in wounds and reduces melanoma growth. Using flow cytometry, we identify CD26/DPP4 as a surface marker that allows isolation of this lineage. Small molecule-based inhibition of CD26/DPP4 enzymatic activity during wound healing results in diminished cutaneous scarring. Identification and isolation of these lineages hold promise for translational medicine aimed at in vivo modulation of fibrogenic behavior.

SUBMITTER: Rinkevich Y

PROVIDER: S-EPMC5088503 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Skin fibrosis. Identification and isolation of a dermal lineage with intrinsic fibrogenic potential.

Rinkevich Yuval Y Walmsley Graham G GG Hu Michael S MS Maan Zeshaan N ZN Newman Aaron M AM Drukker Micha M Januszyk Michael M Krampitz Geoffrey W GW Gurtner Geoffrey C GC Lorenz H Peter HP Weissman Irving L IL Longaker Michael T MT

Science (New York, N.Y.) 20150401 6232

Dermal fibroblasts represent a heterogeneous population of cells with diverse features that remain largely undefined. We reveal the presence of at least two fibroblast lineages in murine dorsal skin. Lineage tracing and transplantation assays demonstrate that a single fibroblast lineage is responsible for the bulk of connective tissue deposition during embryonic development, cutaneous wound healing, radiation fibrosis, and cancer stroma formation. Lineage-specific cell ablation leads to diminish ...[more]

PMID: 25883361

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Project description:Human skin microbiota has been described as a "microbial fingerprint" due to observed differences between individuals. Current understanding of the cutaneous microbiota is based on sampling the outermost layers of the epidermis, while the microbiota in the remaining skin layers has not yet been fully characterized. Environmental conditions can vary drastically between the cutaneous compartments and give rise to unique communities. We demonstrate that the dermal microbiota is surprisingly similar among individuals and contains a specific subset of the epidermal microbiota. Variability in bacterial community composition decreased significantly from the epidermal to the dermal compartment but was similar among anatomic locations (hip and knee). The composition of the epidermal microbiota was more strongly affected by environmental factors than that of the dermal community. These results indicate a well-conserved dermal community that is functionally distinct from the epidermal community, challenging the current dogma. Future studies in cutaneous disorders and chronic infections may benefit by focusing on the dermal microbiota as a persistent microbial community.IMPORTANCE Human skin microbiota is thought to be unique according to the individual's lifestyle and genetic predisposition. This is true for the epidermal microbiota, while our findings demonstrate that the dermal microbiota is universal between healthy individuals. The preserved dermal microbial community is compositionally unique and functionally distinct to the specific environment in the depth of human skin. It is expected to have direct contact with the immune response of the human host, and research in the communication between host and microbiota should be targeted to this cutaneous compartment. This novel insight into specific microbial adaptation can be used advantageously in the research of chronic disorders and infections of the skin. It can enlighten the alteration between health and disease to the benefit of patients suffering from long-lasting socioeconomic illnesses.

Dataset Information

Skin fibrosis. Identification and isolation of a dermal lineage with intrinsic fibrogenic potential.

Publications

Skin fibrosis. Identification and isolation of a dermal lineage with intrinsic fibrogenic potential.

Similar Datasets

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