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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 -
Experimental Dermatology Sep 2014Here, we explore the evolution and development of skin-associated adipose tissue with the goal of establishing nomenclature for this tissue. Underlying the reticular... (Review)
Review
Here, we explore the evolution and development of skin-associated adipose tissue with the goal of establishing nomenclature for this tissue. Underlying the reticular dermis, a thick layer of adipocytes exists that encases mature hair follicles in rodents and humans. The association of lipid-filled cells with the skin is found in many invertebrate and vertebrate species. Historically, this layer of adipocytes has been termed subcutaneous adipose, hypodermis and subcutis. Recent data have revealed a common precursor for dermal fibroblasts and intradermal adipocytes during development. Furthermore, the development of adipocytes in the skin is independent from that of subcutaneous adipose tissue development. Finally, the role of adipocytes has been shown to be relevant for epidermal homoeostasis during hair follicle regeneration and wound healing. Thus, we propose a refined nomenclature for the cells and adipose tissue underlying the reticular dermis as intradermal adipocytes and dermal white adipose tissue, respectively.
Topics: Adipocytes, White; Adipose Tissue, White; Animals; Dermis; Hair Follicle; Humans; Mice; Regeneration; Species Specificity; Subcutaneous Fat; Terminology as Topic; Wound Healing
PubMed: 24841073
DOI: 10.1111/exd.12450 -
Frontiers in Immunology 2019Pemphigoid diseases are a subgroup of autoimmune skin diseases characterized by widespread tense blisters. Standard of care typically involves immunosuppressive... (Review)
Review
Pemphigoid diseases are a subgroup of autoimmune skin diseases characterized by widespread tense blisters. Standard of care typically involves immunosuppressive treatments, which may be insufficient and are often associated with significant adverse events. As such, a deeper understanding of the pathomechanism(s) of pemphigoid diseases is necessary in order to identify improved therapeutic approaches. A major initiator of pemphigoid diseases is the accumulation of autoantibodies against proteins at the dermal-epidermal junction (DEJ), followed by protease activation at the lesion. The contribution of proteases to pemphigoid disease pathogenesis has been investigated using a combination of and models. These studies suggest proteolytic degradation of anchoring proteins proximal to the DEJ is crucial for dermal-epidermal separation and blister formation. In addition, proteases can also augment inflammation, expose autoantigenic cryptic epitopes, and/or provoke autoantigen spreading, which are all important in pemphigoid disease pathology. The present review summarizes and critically evaluates the current understanding with respect to the role of proteases in pemphigoid diseases.
Topics: Autoantibodies; Autoantigens; Dermis; Epidermis; Humans; Pemphigoid, Bullous; Peptide Hydrolases
PubMed: 31297118
DOI: 10.3389/fimmu.2019.01454 -
Developmental Dynamics : An Official... Sep 2007Recent work in teleosts has renewed interest in the dermomyotome, which was initially characterized in the late 19th century. We review the evidence for the teleost... (Review)
Review
Recent work in teleosts has renewed interest in the dermomyotome, which was initially characterized in the late 19th century. We review the evidence for the teleost dermomyotome, comparing it to the more well-characterized amniote dermomyotome. We discuss primary myotome morphogenesis, the relationship between the primary myotome and the dermomyotome, the differentiation of axial muscle, appendicular muscle, and dermis from the dermomyotome, and the signaling molecules that regulate myotome growth from myogenic precursors within the dermomyotome. The recognition of a dermomyotome in teleosts provides a new perspective on teleost muscle growth, as well as a fruitful approach to understanding the vertebrate dermomyotome.
Topics: Animals; Body Patterning; Cell Differentiation; Cell Lineage; Dermis; Developmental Biology; Embryo, Nonmammalian; Fishes; Models, Anatomic; Models, Biological; Muscles; Signal Transduction; Zebrafish
PubMed: 17654604
DOI: 10.1002/dvdy.21253 -
Journal of Anatomy Aug 2019The structure and function of the skin relies on the complex expression pattern and organisation of extracellular matrix macromolecules, of which collagens are a... (Review)
Review
The structure and function of the skin relies on the complex expression pattern and organisation of extracellular matrix macromolecules, of which collagens are a principal component. The fibrillar collagens, types I and III, constitute over 90% of the collagen content within the skin and are the major determinants of the strength and stiffness of the tissue. However, the minor collagens also play a crucial regulatory role in a variety of processes, including cell anchorage, matrix assembly, and growth factor signalling. In this article, we review the expression patterns, key functions and involvement in disease pathogenesis of the minor collagens found in the skin. While it is clear that the minor collagens are important mediators of normal tissue function, homeostasis and repair, further insight into the molecular level structure and activity of these proteins is required for translation into clinical therapies.
Topics: Animals; Basement Membrane; Collagen; Dermis; Humans
PubMed: 31318053
DOI: 10.1111/joa.12584 -
Nan Fang Yi Ke Da Xue Xue Bao = Journal... Mar 2017As a novel population of neural crest-origin precursor cells, skin-derived precursor cells (SKPs) can be isolated from both embryonic and adult dermis. These cells have... (Review)
Review
As a novel population of neural crest-origin precursor cells, skin-derived precursor cells (SKPs) can be isolated from both embryonic and adult dermis. These cells have important values for research and potential clinical application in wound healing, organ regeneration and disease treatment for advantages in the abundance of cell sources, accessibility, potential of multipotent differentiation, and absence of ethical concerns. Here we review the developmental and anatomical origins of SKPs and their potential application in regenerative medicine. SKPs originate from the embryonic neural crest, and their sources may vary in different areas of the body. SKPs are widely found in the dermis, especially in the dermal papilla (DP), which was known as a niche of SKPs. The multipotent SKPs can used for autologous transplantation and are of vital importance in tissue repair.
Topics: Cell Differentiation; Cells, Cultured; Dermis; Humans; Neural Crest; Skin; Stem Cells; Wound Healing
PubMed: 28377365
DOI: 10.3969/j.issn.1673-4254.2017.03.26 -
International Journal of Molecular... Jun 2021Particulate matter with aerodynamic diameter ≤2.5 μm (PM) increases oxidative stress through free radical generation and incomplete volatilization. In addition to...
Particulate matter with aerodynamic diameter ≤2.5 μm (PM) increases oxidative stress through free radical generation and incomplete volatilization. In addition to affecting the respiratory system, PM causes aging- and inflammation-related damage to skin. Farnesol (Farn), a natural benzyl semiterpene, possesses anti-inflammatory, antioxidative, and antibacterial properties. However, because of its poor water solubility and cytotoxicity at high concentrations, the biomedical applications of Farn have been limited. This study examined the deleterious effects of PM on the epidermis and dermis. In addition, Farn-encapsulated liposomes (Lipo-Farn) and gelatin/HA/xanthan gel containing Lipo-Farn were prepared and applied in vivo to repair and alleviate PM-induced damage and inflammation in skin. The prepared Lipo-Farn was 342 ± 90 nm in diameter with an encapsulation rate of 69%; the encapsulation significantly reduced the cytotoxicity of Farn. Lipo-Farn exhibited a slow-release rate of 35% after 192 h of incubation. The half-maximal inhibitory concentration of PM was approximately 850 μg/mL, and ≥400 μg/mL PM significantly increased IL-6 production in skin fibroblasts. Severe impairment in the epidermis and hair follicles and moderate impairment in the dermis were found in the groups treated with post-PM and continuous subcutaneous injection of PM. Acute and chronic inflammation was observed in the skin in both experimental categories in vivo. Treatment with 4 mM Lipo-Farn largely repaired PM-induced injury in the epidermis and dermis, restored injured hair follicles, and alleviated acute and chronic inflammation induced by PM in rat skin. In addition, treatment with 4 mM pure Farn and 2 mM Lipo-Farn exerted moderate reparative and anti-inflammatory effects on impaired skin. The findings of the current study indicate the therapeutic and protective effects of Lipo-Farn against various injuries caused by PM in the pilosebaceous units, epidermis, and dermis of skin.
Topics: Animals; Antioxidants; Dermis; Epidermis; Farnesol; Female; Liposomes; Particulate Matter; Protective Agents; Rats; Rats, Sprague-Dawley; Skin Diseases
PubMed: 34199947
DOI: 10.3390/ijms22116076 -
Science (New York, N.Y.) Nov 2014The skin is our largest sensory organ, transmitting pain, temperature, itch, and touch information to the central nervous system. Touch sensations are conveyed by... (Review)
Review
The skin is our largest sensory organ, transmitting pain, temperature, itch, and touch information to the central nervous system. Touch sensations are conveyed by distinct combinations of mechanosensory end organs and the low-threshold mechanoreceptors (LTMRs) that innervate them. Here we explore the various structures underlying the diverse functions of cutaneous LTMR end organs. Beyond anchoring of LTMRs to the surrounding dermis and epidermis, recent evidence suggests that the non-neuronal components of end organs play an active role in signaling to LTMRs and may physically gate force-sensitive channels in these receptors. Combined with LTMR intrinsic properties, the balance of these factors comprises the response properties of mechanosensory neurons and, thus, the neural encoding of touch.
Topics: Animals; Dermis; Epidermis; Hair; Hair Follicle; Humans; Mechanoreceptors; Mechanotransduction, Cellular; Merkel Cells; Neurons; Pacinian Corpuscles; Touch
PubMed: 25414303
DOI: 10.1126/science.1254229 -
International Journal of Molecular... Jul 2021We studied CD34+ stromal cells/telocytes (CD34+SCs/TCs) in pathologic skin, after briefly examining them in normal conditions. We confirm previous studies by other... (Review)
Review
We studied CD34+ stromal cells/telocytes (CD34+SCs/TCs) in pathologic skin, after briefly examining them in normal conditions. We confirm previous studies by other authors in the normal dermis regarding CD34+SC/TC characteristics and distribution around vessels, nerves and cutaneous annexes, highlighting their practical absence in the papillary dermis and presence in the bulge region of perifollicular groups of very small CD34+ stromal cells. In non-tumoral skin pathology, we studied examples of the principal histologic patterns in which CD34+SCs/TCs have (1) a fundamental pathophysiological role, including (a) fibrosing/sclerosing diseases, such as systemic sclerosis, with loss of CD34+SCs/TCs and presence of stromal cells co-expressing CD34 and αSMA, and (b) metabolic degenerative processes, including basophilic degeneration of collagen, with stromal cells/telocytes in close association with degenerative fibrils, and cutaneous myxoid cysts with spindle-shaped, stellate and bulky vacuolated CD34+ stromal cells, and (2) a secondary reactive role, encompassing dermatitis-e.g., interface (erythema multiforme), acantholytic (pemphigus, Hailey-Hailey disease), lichenoid (lichen planus), subepidermal vesicular (bullous pemphigoid), psoriasiform (psoriasis), granulomatous (granuloma annulare)-vasculitis (leukocytoclastic and lymphocytic vasculitis), folliculitis, perifolliculitis and inflammation of the sweat and sebaceous glands (perifolliculitis and rosacea) and infectious dermatitis (verruca vulgaris). In skin tumor and tumor-like conditions, we studied examples of those in which CD34+ stromal cells are (1) the neoplastic component (dermatofibrosarcoma protuberans, sclerotic fibroma and solitary fibrous tumor), (2) a neoplastic component with varying presentation (fibroepithelial polyp and superficial myxofibrosarcoma) and (3) a reactive component in other tumor/tumor-like cell lines, such as those deriving from vessel periendothelial cells (myopericytoma), epithelial cells (trichoepithelioma, nevus sebaceous of Jadassohn and seborrheic keratosis), Merkel cells (Merkel cell carcinoma), melanocytes (dermal melanocytic nevi) and Schwann cells (neurofibroma and granular cell tumor).
Topics: Animals; Antigens, CD34; Dermatitis; Dermis; Humans; Neoplasm Proteins; Skin Neoplasms; Telocytes
PubMed: 34298962
DOI: 10.3390/ijms22147342 -
Journal of Biomedical Optics Nov 2023Knowledge of optical properties is important to accurately model light propagation in tissue, but reference data are sparse.
SIGNIFICANCE
Knowledge of optical properties is important to accurately model light propagation in tissue, but reference data are sparse.
AIM
The aim of our study was to present skin optical properties from a large Swedish cohort including 3809 subjects using a three-layered skin model and spatially resolved diffuse reflectance spectroscopy (Periflux PF6000 EPOS).
APPROACH
Diffuse reflectance spectra (475 to 850 nm) at 0.4 and 1.2 mm source-detector separations were analyzed using an inverse Monte Carlo method. The model had one epidermis layer with variable thicknesses and melanin-related absorptions and two dermis layers with varying hemoglobin concentrations and equal oxygen saturations. The reduced scattering coefficient was equal across all layers.
RESULTS
Median absorption coefficients () in the upper dermis ranged from 0.094 at 475 nm to 0.0048 at 850 nm and similarly in the lower dermis from 0.059 to 0.0035. The reduced scattering coefficient () ranged from 3.22 to 1.20, and the sampling depth (mm) ranged from 0.23 to 0.38 (0.4 mm separation) and from 0.49 to 0.68 (1.2 mm separation). There were differences in optical properties across sex, age groups, and BMI categories.
CONCLUSIONS
Reference material for skin optical properties is presented.
Topics: Humans; Cohort Studies; Sweden; Models, Biological; Scattering, Radiation; Epidermis; Dermis; Monte Carlo Method
PubMed: 38078153
DOI: 10.1117/1.JBO.28.11.115001