Fine-Structural Identification and Organization of the Epidermal Proliferative Unit

1974 ◽  
Vol 15 (2) ◽  
pp. 291-319
Author(s):  
T. D. ALLEN ◽  
C. S. POTTEN
Keyword(s):  
Central Region ◽  
Cell Attachment ◽  
Basal Layer ◽  
Structural Identification ◽  
Basal Cells ◽  
Vertical Column ◽  
Vertical Organization ◽  
Interfollicular Epidermis ◽  
Spinous Layer ◽  
Overlapping Region

Mouse dorsal interfollicular epidermis has a vertical organization consisting of approximately 1400 units/mm2. Each unit is identified by its uppermost 4 to 6 layers of roughly hexagonal flattened cornified cells or squames, which are stacked in a precise vertical column. Beneath each column of squames there are 3 differentiating cells and a group of 10 or 11 basal cells, which provide cells to replace those lost by desquamation at the top of the squame column. The whole unit is termed an epidermal proliferative unit or EPU. In the central region of the basal layer of each EPU is a single dendritic Langerhans cell, devoid of desmosomes, but held in position by the surrounding keratinocytes. The dendrites radiate outwards between the keratinocytes to the periphery of the unit. Keratinocyte migration into the spinous layer takes place from the edge of the unit. In the squame column itself, a modified cell-to-cell attachment (squamosome) runs around the edge of each cornified cell, and attaches it to the overlapping region of cells from adjacent squame columns.

scholarly journals Role of Jagged1-mediated Notch Signaling Activation in the Differentiation and Stratification of the Human Limbal Epithelium

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1945
Author(s):  
Sheyla González ◽  
Maximilian Halabi ◽  
David Ju ◽  
Matthew Tsai ◽  
Sophie X. Deng
Keyword(s):  
Notch Signaling ◽  
Progenitor Cell ◽  
Basal Layer ◽  
Notch Signaling Pathway ◽  
Basal Cells ◽  
Proliferation Markers ◽  
Limbal Epithelium ◽  
Asymmetric Divisions ◽  
Signaling Activation

The Notch signaling pathway plays a key role in proliferation and differentiation. We investigated the effect of Jagged 1 (Jag1)-mediated Notch signaling activation in the human limbal stem/progenitor cell (LSC) population and the stratification of the limbal epithelium in vitro. After Notch signaling activation, there was a reduction in the amount of the stem/progenitor cell population, epithelial stratification, and expression of proliferation markers. There was also an increase of the corneal epithelial differentiation. In the presence of Jag1, asymmetric divisions were decreased, and the expression pattern of the polarity protein Par3, normally present at the apical-lateral membrane of basal cells, was dispersed in the cells. We propose a mechanism in which Notch activation by Jag1 decreases p63 expression at the basal layer, which in turn reduces stratification by decreasing the number of asymmetric divisions and increases differentiation.

scholarly journals Effects of a 10% carbamide peroxide bleaching agent on rat oral epithelium proliferation

2002 ◽  
Vol 13 (3) ◽  
pp. 162-165 ◽  
Author(s):  
Rodrigo de Castro Albuquerque ◽  
Ricardo Santiago Gomez ◽  
Rodrigo Aliprandi Dutra ◽  
Wallison Arthuso Vasconcellos ◽  
Renato Santiago Gomez ◽  
...  
Keyword(s):  
Oral Mucosa ◽  
Topical Application ◽  
Basal Layer ◽  
Nuclear Antigen ◽  
Oral Epithelium ◽  
Basal Cells ◽  
Immunohistochemical Expression ◽  
Carbamide Peroxide ◽  
Peroxide Bleaching ◽  
Short Course

The purpose of the present study was to evaluate the influence of short course topical application of carbamide peroxide on proliferating cell nuclear antigen (PCNA) immunohistochemical expression in the oral tongue mucosa of rats. Twelve male Wistar rats were submitted to topical application of 10% carbamide peroxide on one side of the dorsal tongue once a week for three consecutive weeks. Only distilled water was applied on the control side. The animals were killed on days 0, 10, and 20 after the last application. The tongue was fixed in buffered formalin for 24 h and embedded in paraffin. Tissue blocks (3 µm) were subjected to the biotin-streptavidin amplified system for identification of PCNA. The percentage of epithelial-positive basal cells in each side of the tongue mucosa was calculated. The results demonstrated that topical application of 10% carbamide peroxide increases PCNA immunohistochemical expression on the basal layer of the oral mucosa epithelium of rats on day 0 after treatment. In conclusion, short-course use of carbamide peroxide induces transient epithelial cell proliferation of the oral mucosa of rats.

scholarly journals CK20 and CK5/6 Immunohistochemical Staining of Urothelial Neoplasms: A Perspective

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Mohammed Akhtar ◽  
Sameera Rashid ◽  
Mohamed Ben Gashir ◽  
Noheir Mostafa Taha ◽  
Issam Al Bozom
Keyword(s):  
Mechanical Stability ◽  
Basal Layer ◽  
Low Grade ◽  
High Grade ◽  
Basal Cells ◽  
The Family ◽  
Prognostic Implications ◽  
Umbrella Cells ◽  
Proper Interpretation ◽  
Aggressive Clinical Behavior

Cytokeratins belong to the family of intermediate filaments. They are expressed in a highly specific manner in epithelial cells where they play a crucial role in the integrity and mechanical stability of the cells. Several types of cytokeratins have been described in normal as well as neoplastic urothelium. In the case of urothelial neoplasms expression of CK20 and CK5/6 has been shown in several studies to have diagnostic and prognostic implications. Thus, low-grade urothelial carcinoma manifests CK expression limited to the umbrella cells, while high-grade tumors usually have an expression in the entire thickness of the urothelium except for the basal layer. CK5/6 expression on the other hand is expressed in the basal cells in all low-grade and some high-grade urothelial carcinomas. Diffuse CK20 staining accompanied by loss of CK5/6-positive basal layer is usually associated with aggressive clinical behavior. Double staining of the slides for these cytokeratins may facilitate proper interpretation and correlation.

scholarly journals Advanced Verrucous Squamous Cell Carcinoma of the Esophagus: Case Report and Literature Review

2017 ◽  
Author(s):  
Nobuhisa Takase ◽  
Satoshi Suzuki ◽  
Tetsu Nakamura ◽  
Masashi Yamamoto ◽  
Shingo Kanaji ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Basal Layer ◽  
Esophageal Tumor ◽  
Basal Cells ◽  
Histological Findings ◽  
Carcinoma Of The Esophagus ◽  
Verrucous Squamous Cell Carcinoma ◽  
Well Differentiated

Abstract Verrucous squamous cell carcinoma (VSCC) is a rare esophageal tumor histologically defined as a well-differentiated subtype. We present a rare case that was diagnosed as esophageal VSCC preoperatively. A 62-year-old Japanese male was referred to our hospital for further evaluation, presenting with anorexia and postcibal vomiting. An esophagogastroduodenoscopy (EGD) examination showed esophageal stricture with white-colored papillary nodules in the lower esophagus. We performed repeated superficial endoscopic biopsies of the lesion, but the histological findings showed nonspecific changes. With an endoscopic boring biopsy, the lesion showed an endophytic growth pattern, well-differentiated SCC with minimal cellular atypia and rare mitosis, and mature squamous epithelium with extensive keratinization. We preoperatively diagnosed the lesion as esophageal VSCC, and we performed a video-assisted thoracoscopic subtotal esophagectomy and cardiectomy with the patient in the prone position. Histological findings revealed that the invasive well-differentiated SCC extended into the esophageal adventitia and the stomach wall with a pushing border. Regional lymph node metastasis and vascular invasion were negative. The expression of Ki-67 was distributed mainly in the basal cells rather than parabasal cells. Without a conclusive diagnosis, a certain degree of diagnostic prediction is possible by understanding the clinical manifestations, macroscopic form and histology around the basal cells. It is helpful to obtain the high accuracy provided by an endoscopic biopsy including the basal layer in order to avoid the diagnostic dilemma that is often presented by esophageal VSCC.

scholarly journals Pathogenesis of Human Papillomaviruses in Differentiating Epithelia

2004 ◽  
Vol 68 (2) ◽  
pp. 362-372 ◽  
Author(s):  
Michelle S. Longworth ◽  
Laimonis A. Laimins
Keyword(s):  
Life Cycle ◽  
Genital Tract ◽  
Basal Layer ◽  
Viral Life Cycle ◽  
Human Papillomaviruses ◽  
Basal Cells ◽  
Human Pathogens ◽  
Late Gene Expression ◽  
Differentiated Cells ◽  
Hpv Types

SUMMARY Human papillomaviruses (HPV) are the etiological agents of cervical and other anogenital malignancies. Over 100 different types of HPVs have been identified to date, and all target epithelial tissues for infection. One-third of HPV types specifically infect the genital tract, and a subset of these are the causative agents of anogenital cancers. Other HPV types that infect the genital tract induce benign hyperproliferative lesions or genital warts. The productive life cycle of HPVs is linked to epithelial differentiation. Papillomaviruses are thought to infect cells in the basal layer of stratified epithelia and establish their genomes as multicopy nuclear episomes. In these cells, viral DNA is replicated along with cellular chromosomes. Following cell division, one of the daughter cells migrates away from the basal layer and undergoes differentiation. In highly differentiated suprabasal cells, vegetative viral replication and late-gene expression are activated, resulting in the generation of progeny virions. Since virion production is restricted to differentiated cells, infected basal cells can persist for up to several decades or until the immune system clears the infection. The E6 and E7 genes encode viral oncoproteins that target Rb and p53, respectively. During the viral life cycle, these proteins facilitate stable maintenance of episomes and stimulate differentiated cells to reenter the S phase. The E1 and E2 proteins act as origin recognition factors as well as regulators of early viral transcription. The functions of the E5 and E1^E4 proteins are still largely unknown, but these proteins have been implicated in modulating late viral functions. The L1 and L2 proteins form icosahedral capsids for progeny virion generation. The characterization of the cellular targets of these viral proteins and the mechanisms regulating the differentiation-dependent viral life cycle remain active areas for the study of these important human pathogens.

Reconstructed interfollicular feline epidermis as a model for Microsporum canis dermatophytosis

2007 ◽  
Vol 56 (7) ◽  
pp. 971-975 ◽  
Author(s):  
Jeremy Tabart ◽  
Aline Baldo ◽  
Sandy Vermout ◽  
Betty Nusgens ◽  
Charles Lapiere ◽  
...  
Keyword(s):  
Histological Analysis ◽  
Pathogenic Fungus ◽  
Basal Layer ◽  
Histopathological Analysis ◽  
Microsporum Canis ◽  
Living Tissue ◽  
Cutaneous Infection ◽  
Interfollicular Epidermis

Microsporum canis is a pathogenic fungus that causes a superficial cutaneous infection called dermatophytosis. The complexity of mechanisms involved in dermatophytic infections makes relevant in vivo studies particularly difficult to perform. The aim of this study was to develop a new in vitro model of M. canis dermatophytosis using feline fetal keratinocytes in reconstructed interfollicular epidermis, and to investigate its relevance in studying the host–pathogen relationship. Histological analysis of reconstructed interfollicular feline epidermis (RFE) revealed a fully differentiated epidermis. A proliferation assay showed replicating cells only in the basal layer, indicating that RFE is a well-stratified living tissue, leading to the formation of a horny layer. Histopathological analysis of RFE infected by M. canis arthroconidia revealed that the fungus invades the stratum corneum and produces SUB3, a keratinase implicated in the infectious process. In view of these results, an M. canis dermatophytosis model on RFE seems to be a useful tool to investigate mechanisms involved in natural M. canis feline infections.

scholarly journals Type XVII collagen coordinates proliferation in the interfollicular epidermis

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Mika Watanabe ◽  
Ken Natsuga ◽  
Wataru Nishie ◽  
Yasuaki Kobayashi ◽  
Giacomo Donati ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Physical Aging ◽  
Transmembrane Protein ◽  
Aged Mouse ◽  
Basal Cells ◽  
Junctional Epidermolysis Bullosa ◽  
Kinase C ◽  
Interfollicular Epidermis ◽  
Aged Skin ◽  
Xvii Collagen

Type XVII collagen (COL17) is a transmembrane protein located at the epidermal basement membrane zone. COL17 deficiency results in premature hair aging phenotypes and in junctional epidermolysis bullosa. Here, we show that COL17 plays a central role in regulating interfollicular epidermis (IFE) proliferation. Loss of COL17 leads to transient IFE hypertrophy in neonatal mice owing to aberrant Wnt signaling. The replenishment of COL17 in the neonatal epidermis of COL17-null mice reverses the proliferative IFE phenotype and the altered Wnt signaling. Physical aging abolishes membranous COL17 in IFE basal cells because of inactive atypical protein kinase C signaling and also induces epidermal hyperproliferation. The overexpression of human COL17 in aged mouse epidermis suppresses IFE hypertrophy. These findings demonstrate that COL17 governs IFE proliferation of neonatal and aged skin in distinct ways. Our study indicates that COL17 could be an important target of anti-aging strategies in the skin.

scholarly journals Biological Assessment of Zn–Based Absorbable Metals for Ureteral Stent Applications

Materials ◽  
2019 ◽  
Vol 12 (20) ◽  
pp. 3325 ◽  
Author(s):  
Devi Paramitha ◽  
Stéphane Chabaud ◽  
Stéphane Bolduc ◽  
Hendra Hermawan
Keyword(s):  
Urinary Tract Obstruction ◽  
Basal Layer ◽  
Superficial Layer ◽  
Biological Assessment ◽  
Basal Cells ◽  
Ureteral Stents ◽  
Urothelial Cells ◽  
Cytoskeletal Networks ◽  
2D And 3D ◽  
Tissue Construct

The use of ureteral stents to relieve urinary tract obstruction is still challenged by the problems of infection, encrustation, and compression, leading to the need for early removal procedures. Biodegradable ureteral stents, commonly made of polymers, have been proposed to overcome these problems. Recently, absorbable metals have been considered as potential materials offering both biodegradation and strength. This work proposed zinc-based absorbable metals by firstly evaluating their cytocompatibility toward normal primary human urothelial cells using 2D and 3D assays. In the 2D assay, the cells were exposed to different concentrations of metal extracts (i.e., 10 mg/mL of Zn–1Mg and 8.75 mg/mL of Zn–0.5Al) for up to 3 days and found that their cytoskeletal networks were affected but were recovered at day 3, as observed by immunofluorescence. In the 3D ureteral wall tissue construct, the cells formed a multilayered urothelium, as found in native tissue, with the presence of tight junctions at the superficial layer and laminin at the basal layer, indicating a healthy tissue condition even with the presence of the metal samples for up to 7 days of exposure. The basal cells attached to the metal surface as seen in a natural spreading state with pseudopodia and fusiform morphologies, indicating that the metals were non-toxic.

Label-retaining cells of the bladder: candidate urothelial stem cells

2008 ◽  
Vol 294 (6) ◽  
pp. F1415-F1421 ◽  
Author(s):  
Eric A. Kurzrock ◽  
Deborah K. Lieu ◽  
Lea A. deGraffenried ◽  
Camie W. Chan ◽  
Roslyn R. Isseroff
Keyword(s):  
Stem Cells ◽  
Basal Layer ◽  
Basal Cells ◽  
Bladder Epithelium ◽  
Chase Period ◽  
Brdu Label ◽  
Dividing Cells ◽  
Β4 Integrin ◽  
Cytokeratin 14

Adult tissue stem cells replicate infrequently, retaining DNA nucleotide label (BrdU) for much longer periods than mature, dividing cells in which the label is diluted during a chase period. Those “label-retaining cells” (LRCs) have been identified as the tissue stem cells in skin, cornea, intestine, and prostate. However, in the urinary tract uroepithelial stem cells have not yet been identified. In this study, BrdU administration identified urothelial LRCs in the rat bladder with 9% of the epithelial basal cells retaining BrdU label 1 yr after its administration. Markers for stem cells in other tissues, Bcl, p63, cytokeratin 14, and β1 integrin, were immunolocalized in the basal bladder epithelium in or near urothelial LRCs, but not uniquely limited to these cells. Flow cytometry demonstrated that urothelial LRCs were small, had low granularity, and were uniquely β4 integrin bright. Urothelium from long-term labeled bladders was cultured and LRCs were found to be significantly more clonogenic and proliferative, characteristics of stem cells, than unlabeled urothelial cells. Thus, this work demonstrates that LRCs in the bladder localize to the basal layer, are small, low granularity, uniquely β4 integrin rich, slowly cycling and demonstrate superior clonogenic and proliferative ability compared with unlabeled epithelial cells. We propose that LRCs represent putative urothelial stem cells.

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