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Cells Jun 2019There are many studies on certain skin cell specifications and their contribution to wound healing. In this review, we provide an overview of dermal cell heterogeneity... (Review)
Review
There are many studies on certain skin cell specifications and their contribution to wound healing. In this review, we provide an overview of dermal cell heterogeneity and their participation in skin repair, scar formation, and in the composition of skin substitutes. The papillary, reticular, and hair follicle associated fibroblasts differ not only topographically, but also functionally. Human skin has a number of particular characteristics that are different from murine skin. This should be taken into account in experimental procedures. Dermal cells react differently to skin wounding, remodel the extracellular matrix in their own manner, and convert to myofibroblasts to different extents. Recent studies indicate a special role of papillary fibroblasts in the favorable outcome of wound healing and epithelial-mesenchyme interactions. Neofolliculogenesis can substantially reduce scarring. The role of hair follicle mesenchyme cells in skin repair and possible therapeutic applications is discussed. Participation of dermal cell types in wound healing is described, with the addition of possible mechanisms underlying different outcomes in embryonic and adult tissues in the context of cell population characteristics and extracellular matrix composition and properties. Dermal white adipose tissue involvement in wound healing is also overviewed. Characteristics of myofibroblasts and their activity in scar formation is extensively discussed. Cellular mechanisms of scarring and possible ways for its prevention are highlighted. Data on keloid cells are provided with emphasis on their specific characteristics. We also discuss the contribution of tissue tension to the scar formation as well as the criteria and effectiveness of skin substitutes in skin reconstruction. Special attention is given to the properties of skin substitutes in terms of cell composition and the ability to prevent scarring.
Topics: Animals; Cicatrix; Dermis; Extracellular Matrix; Fibroblasts; Hair Follicle; Humans; Keloid; Myofibroblasts; Regeneration; Skin; Skin Physiological Phenomena; Skin, Artificial; Wound Healing
PubMed: 31216669
DOI: 10.3390/cells8060607 -
The Journal of Clinical Investigation Jan 2018Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining the structural integrity of most tissues. Researchers have... (Review)
Review
Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining the structural integrity of most tissues. Researchers have long suspected that fibroblasts exhibit functional specialization according to their organ of origin, body site, and spatial location. In recent years, a number of approaches have revealed the existence of fibroblast subtypes in mice. Here, we discuss fibroblast heterogeneity with a focus on the mammalian dermis, which has proven an accessible and tractable system for the dissection of these relationships. We begin by considering differences in fibroblast identity according to anatomical site of origin. Subsequently, we discuss new results relating to the existence of multiple fibroblast subtypes within the mouse dermis. We consider the developmental origin of fibroblasts and how this influences heterogeneity and lineage restriction. We discuss the mechanisms by which fibroblast heterogeneity arises, including intrinsic specification by transcriptional regulatory networks and epigenetic factors in combination with extrinsic effects of the spatial context within tissue. Finally, we discuss how fibroblast heterogeneity may provide insights into pathological states including wound healing, fibrotic diseases, and aging. Our evolving understanding suggests that ex vivo expansion or in vivo inhibition of specific fibroblast subtypes may have important therapeutic applications.
Topics: Animals; Dermis; Epigenesis, Genetic; Fibroblasts; Gene Expression Regulation, Neoplastic; Humans; Skin Neoplasms; Transcription, Genetic
PubMed: 29293096
DOI: 10.1172/JCI93555 -
Wiley Interdisciplinary Reviews.... Mar 2018The skin is the largest organ of the body and is composed of two layers: the overlying epidermis and the underlying dermis. The dermal fibroblasts originate from... (Review)
Review
The skin is the largest organ of the body and is composed of two layers: the overlying epidermis and the underlying dermis. The dermal fibroblasts originate from distinct locations of the embryo and contain the positional identity and patterning information in the skin. The dermal fibroblast progenitors differentiate into various cell types that are fated to perform specific functions such as hair follicle initiation and scar formation during wound healing. Recent studies have revealed the heterogeneity and plasticity of dermal fibroblasts within skin, which has implications for skin disease and tissue engineering. The objective of this review is to frame our current understanding and provide new insights on the origin and differentiation of dermal fibroblasts and their function during cutaneous development and healing. WIREs Dev Biol 2018, 7:e307. doi: 10.1002/wdev.307 This article is categorized under: Birth Defects > Organ Anomalies Signaling Pathways > Cell Fate Signaling Adult Stem Cells, Tissue Renewal, and Regeneration > Regeneration Nervous System Development > Vertebrates: Regional Development.
Topics: Animals; Cell Differentiation; Cicatrix; Dermis; Embryonic Stem Cells; Fibroblasts; Humans
PubMed: 29244903
DOI: 10.1002/wdev.307 -
Mechanisms of Ageing and Development Jan 2019Ageing is today a major societal concern that is intrinsically associated with the increase of life expectancy. Outside the context of severe degenerative diseases that... (Review)
Review
Ageing is today a major societal concern that is intrinsically associated with the increase of life expectancy. Outside the context of severe degenerative diseases that affect the elderly populations, normal visible signs of ageing, notably skin sagging and wrinkles, influence the social and individual perception of peoples. Accordingly, there is a strong demand for researches on skin ageing. Deciphering the cellular and molecular processes of skin evolution through ageing is thus an active scientific domain, at the frontier of tissue developmental and ageing biology. The focus of the present article is to provide an overview of the current knowledge concerning the evolution of dermis characteristics at different life stages, from intra-uterine to post-natal life. The description will integrate stage-specific and age-related changes in dermis characteristics at the tissue, cell, and molecular levels.
Topics: Aging; Animals; Dermis; Extracellular Matrix; Humans; Skin Aging
PubMed: 29548941
DOI: 10.1016/j.mad.2018.03.006 -
Theranostics 2021Vascular endothelial cells (ECs) are increasingly recognized as active players in intercellular crosstalk more than passive linings of a conduit for nutrition delivery.... (Comparative Study)
Comparative Study
Vascular endothelial cells (ECs) are increasingly recognized as active players in intercellular crosstalk more than passive linings of a conduit for nutrition delivery. Yet, their functional roles and heterogeneity in skin remain uncharacterized. We have used single-cell RNA sequencing (scRNA-seq) as a profiling strategy to investigate the tissue-specific features and intra-tissue heterogeneity in dermal ECs at single-cell level. Skin tissues collected from 10 donors were subjected to scRNA-seq. Human dermal EC atlas of over 23,000 single-cell transcriptomes was obtained and further analyzed. Arteriovenous markers discovered in scRNA-seq were validated in human skin samples via immunofluorescence. To illustrate tissue-specific characteristics of dermal ECs, ECs from other human tissues were extracted from previously reported data and compared with our transcriptomic data. In comparison with ECs from other human tissues, dermal ECs possess unique characteristics in metabolism, cytokine signaling, chemotaxis, and cell adhesions. Within dermal ECs, 5 major subtypes were identified, which varied in molecular signatures and biological activities. Metabolic transcriptome analysis revealed a preference for oxidative phosphorylation in arteriole ECs when compared to capillary and venule ECs. Capillary ECs abundantly expressed HLA-II molecules, suggesting its immune-surveillance role. Post-capillary venule ECs, with high levels of adhesion molecules, were equipped with the capacity in immune cell arrest, adhesion, and infiltration. Our study provides a comprehensive characterization of EC features and heterogeneity in human dermis and sets the stage for future research in identifying disease-specific alterations of dermal ECs in various dermatoses.
Topics: Base Sequence; Biomarkers; Capillaries; Cell Adhesion; Dermis; Endothelial Cells; Gene Expression; Humans; Phenotype; Single-Cell Analysis; Transcriptome; Venules
PubMed: 33995668
DOI: 10.7150/thno.54917 -
Frontiers in Immunology 2022Fibrotic scars are common in both human and mouse skin wounds. However, wound-induced hair neogenesis in the murine wounding models often results in regenerative repair...
BACKGROUND
Fibrotic scars are common in both human and mouse skin wounds. However, wound-induced hair neogenesis in the murine wounding models often results in regenerative repair response. Herein, we aimed to uncover cellular functional heterogeneity in dermis between fibrotic and regenerative wound healing fates.
METHODS
The expression matrix of single-cell RNA sequencing (scRNA-seq) data of fibrotic and regenerative wound dermal cells was filtered, normalized, and scaled; underwent principal components analysis; and further analyzed by Uniform Manifold Approximation and Projection (UMAP) for dimension reduction with the Seurat package. Cell types were annotated, and cell-cell communications were analyzed. The core cell population myofibroblast was identified and the biological functions of ligand and receptor genes between myofibroblast and macrophage were evaluated. Specific genes between fibrotic and regenerative myofibroblast and macrophage were identified. Temporal dynamics of myofibroblast and macrophage were reconstructed with the Monocle tool.
RESULTS
Across dermal cells, there were six cell types, namely, EN1-negative myofibroblasts, EN1-positive myofibroblasts, hematopoietic cells, macrophages, pericytes, and endothelial cells. Ligand and receptor genes between myofibroblasts and macrophages mainly modulated cell proliferation and migration, tube development, and the TGF-β pathway. Specific genes that were differentially expressed in fibrotic compared to regenerative myofibroblasts or macrophages were separately identified. Specific genes between fibrotic and regenerative myofibroblasts were involved in the mRNA metabolic process and organelle organization. Specific genes between fibrotic and regenerative macrophages participated in regulating immunity and phagocytosis. We then observed the underlying evolution of myofibroblasts or macrophages.
CONCLUSION
Collectively, our findings reveal that myofibroblasts and macrophages may alter the skin wound healing fate through modulating critical signaling pathways.
Topics: Animals; Dermis; Endothelial Cells; Fibrosis; Ligands; Mice; Sequence Analysis, RNA; Wound Healing
PubMed: 35664010
DOI: 10.3389/fimmu.2022.875407 -
Nature Nov 2018
Topics: Acne Vulgaris; Adolescent; Dermatitis; Dermis; Epidermis; Hair; Humans; Melanoma; Sensory Receptor Cells; Skin; Skin Neoplasms; Skin Physiological Phenomena; Subcutaneous Fat; Touch; Touch Perception; Young Adult
PubMed: 30464287
DOI: 10.1038/d41586-018-07429-3 -
Methods in Molecular Biology (Clifton,... 2020The skin contains three primary layers: epidermis, dermis, and hypodermis. Separation of epidermal components from the dermis (dermal-epidermal separation) is an...
The skin contains three primary layers: epidermis, dermis, and hypodermis. Separation of epidermal components from the dermis (dermal-epidermal separation) is an important basic investigation technique for pharmacology, toxicology, and biology. There are different systems of epidermal separation, including typical methods of chemical, enzyme, heat, etc. Each approach has advantages versus disadvantages, and thus the appropriate method should be chosen for a given research question. Here we described the method of heat separation.
Topics: Cell Separation; Dermis; Epidermal Cells; Hot Temperature; Humans; Skin
PubMed: 31792755
DOI: 10.1007/7651_2019_270 -
Methods in Molecular Biology (Clifton,... 2020The skin contains three primary layers: epidermis, dermis, and hypodermis. Separation of epidermal components from dermis (dermal-epidermal separation) is an important...
The skin contains three primary layers: epidermis, dermis, and hypodermis. Separation of epidermal components from dermis (dermal-epidermal separation) is an important basic investigation technique for pharmacology, toxicology, and biology. There are different systems of epidermal separation, including typical methods of chemical, enzyme, heat, etc. Each approach has advantages versus disadvantages, and thus the appropriate method should be chosen for a given research question. Here we described the method of chemical separation.
Topics: Cell Separation; Dermis; Epidermal Cells; Humans; Skin; Thiocyanates
PubMed: 31792754
DOI: 10.1007/7651_2019_266 -
Archives of Dermatological Research Jan 2018Dermal-epidermal separation is an important basic investigation technique for pharmacology, toxicology and biology. To choose the optimal method for a given research... (Comparative Study)
Comparative Study Review
Dermal-epidermal separation is an important basic investigation technique for pharmacology, toxicology and biology. To choose the optimal method for a given research need, we reviewed studies on epidermal separation. PubMed, Embase, and Web of Science were utilized. Different separation systems have been compared, including chemical, enzyme, heat and mechanical separation; each has advantages and disadvantages. Heat is simple but causes thermal damage. Chemical reagents are effective but disturb cellular electrolyte equilibrium. Enzymes provide complete separation, but destroy important components. Mechanical division does not alter physical and/or chemical integrity, but necessitates a relatively large sample and may cause cross-contamination of layers. Thus, the appropriate method should be chosen for a given research question, and no single method appears superior for all purposes.
Topics: Biomedical Research; Cell Separation; Dermis; Epidermal Cells; Humans
PubMed: 28936624
DOI: 10.1007/s00403-017-1774-8