The Experts below are selected from a list of 264 Experts worldwide ranked by ideXlab platform
Fiona M Watt - One of the best experts on this subject based on the ideXlab platform.
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19 Epidermal Stem Cells
Cold Spring Harbor Monograph Archive, 2001Co-Authors: Fiona M WattAbstract:The epidermis of mammals forms the outer covering of the skin and comprises both the interfollicular epidermis and the adnexal structures, such as the hairs and sebaceous glands (Odland 1991). The major cell type in the epidermis is an epithelial cell called a keratinocyte. Interfollicular epidermis is made up of multiple Layers of keratinocytes. The Basal Layer of cells, attached to the underlying basement membrane, contains keratinocytes that are capable of dividing, and cells that leave the Basal Layer undergo a process of terminal differentiation as they move toward the surface of the skin. The end point of this pathway is an anucleate cell, called a squame, which is filled with insoluble, transglutaminase-crosslinked protein and provides an effective barrier between the environment and the underlying living Layers of the skin. The Basal Layer of interfollicular keratinocytes is continuous with the Basal Layer of keratinocytes that form the hair follicles and sebaceous glands; once again, the end point of terminal differentiation is a dead, highly specialized cell, forming the hair shaft or the lipid-filled sebocytes. If stem cells are defined as cells with the capacity for unlimited self-renewal and also the ability to generate daughter cells that undergo terminal differentiation (Hall and Watt 1989; Watt 1998; Watt and Hogan 2000), then the epidermis is one of the tissues in which a stem cell compartment must be present. Throughout adult life there is a requirement for the production of new interfollicular keratinocytes to replace the squames that are continually being shed from...
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the spatial relationship between stem cells and their progeny in the Basal Layer of human epidermis a new view based on whole mount labelling and lineage analysis
Development, 1999Co-Authors: Uffe Birk Jensen, Sally Lowell, Fiona M WattAbstract:In order to examine the spatial organisation of stem cells and their progeny in human epidermis, we developed a method for whole-mount epidermal immunofluorescence labelling using high surface beta1 integrin expression as a stem cell marker. We confirmed that there are clusters of high beta1 integrin-expressing cells at the tips of the dermal papillae in epidermis from several body sites, whereas alpha6 integrin expression is more uniform. The majority of actively cycling cells detected by Ki67 or bromodeoxyuridine labelling were found in the beta1 integrin-dull, transit amplifying population and integrin-negative, keratin 10-positive cells left the Basal Layer exclusively from this compartment. When we examined p53-positive clones in sun-exposed epidermis, we found two types of clone that differed in size and position in a way that was consistent with the founder cell being a stem or transit amplifying cell. The patterning of the Basal Layer implies that transit amplifying cells migrate over the basement membrane away from the stem cell clusters. In support of this, isolated beta1 integrin-dull keratinocytes were more motile on type IV collagen than beta1 integrin-bright keratinocytes and EGFP-labelled stem cell clones in confluent cultured sheets were compact, whereas transit amplifying clones were dispersed. The combination of whole-mount labelling and lineage marking thus reveals features of epidermal organisation that were previously unrecognised.
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epidermal stem cells markers patterning and the control of stem cell fate
Philosophical Transactions of the Royal Society B, 1998Co-Authors: Fiona M WattAbstract:Within the epidermis, proliferation takes place in the Basal Layer of keratinocytes that are attached to an underlying basement membrane. Cells that leave the Basal Layer undergo terminal differentiation as they move towards the tissue surface. The Basal Layer contains two types of proliferative keratinocyte: stem cells, which have unlimited self-renewal capacity, and transit amplifying cells, those daughters of stem cells that are destined to withdraw from the cell cycle and terminally differentiate after a few rounds of division. Stem cells express higher levels of the beta 1-integrin family of extracellular matrix receptors than transit amplifying cells and this can be used to isolate each subpopulation of keratinocyte and to determine its location within the epidermis. Variation in the levels of E-cadherin, beta-catenin and plakoglobin within the Basal Layer suggests that stem cells may also differ from transit amplifying cells in intercellular adhesiveness. Stem cells have a patterned distribution within the epidermal Basal Layer and patterning is subject to autoregulation. Constitutive expression of the transcription factor c-Myc promotes terminal differentiation by driving keratinocytes from the stem cell compartment into the transit amplifying compartment.
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Epidermal stem cells: markers, patterning and the control of stem cell fate.
Philosophical Transactions of the Royal Society B, 1998Co-Authors: Fiona M WattAbstract:Within the epidermis, proliferation takes place in the Basal Layer of keratinocytes that are attached to an underlying basement membrane. Cells that leave the Basal Layer undergo terminal differentiation as they move towards the tissue surface. The Basal Layer contains two types of proliferative keratinocyte: stem cells, which have unlimited self–renewal capacity, and transit amplifying cells, those daughters of stem cells that are destined to withdraw from the cell cycle and terminally differentiate after a few rounds of division. Stem cells express higher levels of the β1–integrin family of extracellular matrix receptors than transit amplifying cells and this can be used to isolate each subpopulation of keratinocyte and to determine its location within the epidermis. Variation in the levels of E–cadherin, β–catenin and plakoglobin within the Basal Layer suggests that stem cells may also differ from transit amplifying cells in intercellular adhesiveness. Stem cells have a patterned distribution within the epidermal Basal Layer and patterning is subject to autoregulation. Constitutive expression of the transcription factor c–Myc promotes terminal differentiation by driving keratinocytes from the stem cell compartment into the transit amplifying compartment.
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the epidermal stem cell compartment variation in expression levels of e cadherin and catenins within the Basal Layer of human epidermis
Journal of Histochemistry and Cytochemistry, 1997Co-Authors: Jeanpierre Moles, Fiona M WattAbstract:SUMMARY The Basal Layer of the epidermis contains two types of proliferating keratinocyte: stem cells, with high proliferative potential, and transit amplifying cells, which are destined to undergo terminal differentiation after a few rounds of division. It has been shown previously that two- to three-fold differences in the average staining intensity of fluorescein-conjugated antibodies to � 1 integrin subunits reflect profound differences in the proliferative potential of keratinocytes, with integrin-bright populations being enriched for stem cells. In the search for additional stem cell markers, we have stained sections of normal human epidermis with antibodies to proteins involved in intercellular adhesion and quantitated the fluorescence of individual cell–cell borders. In the Basal Layer, patches of brightly labeled cells were detected with antibodies to E-cadherin, � -catenin, and � -catenin, but not with antibodies to P-cadherin, � -catenin, or with pan-desmocollin and pan-desmoglein antibodies. In the body sites examined, palm and foreskin, integrinbright regions were strongly labeled for � -catenin and weakly labeled for E-cadherin and � -catenin. Our data suggest that there are gradients of both cell–cell and cell–extracellular matrix adhesiveness within the epidermal Basal Layer and that the levels of E-cadherin and of � -and � -catenin may provide markers for the stem cell compartment, stem cells expressing relatively higher levels of � -catenin and lower levels of E-cadherin and � -catenin than other Basal keratinocytes. (J Histochem Cytochem 45:867–874, 1997)
Marie Wagle - One of the best experts on this subject based on the ideXlab platform.
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r spondin1 protects mice from chemotherapy or radiation induced oral mucositis through the canonical wnt β catenin pathway
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Jingsong Zhao, Josephine De Vera, Servando Palencia, Marie WagleAbstract:R-Spondin1 (RSpo1) is a novel secreted protein that augments canonical Wnt/β-catenin signaling. We injected recombinant RSpo1 protein into transgenic Wnt reporter TOPGAL mice and have identified the oral mucosa as a target tissue for RSpo1. Administration of RSpo1 into normal mice triggered nuclear translocation of β-catenin and resulted in increased Basal Layer cellularity, thickened mucosa, and elevated epithelial cell proliferation in tongue. We herein evaluated the therapeutic potential of RSpo1 in treating chemotherapy or radiotherapy-induced oral mucositis in several mouse models. Prophylactic treatment with RSpo1 dose-dependently overcame the reduction of Basal Layer epithelial cellularity, mucosal thickness, and epithelial cell proliferation in tongues of mice exposed to whole-body irradiation. RSpo1 administration also substantially alleviated tongue mucositis in the oral cavity of mice receiving concomitant 5-fluorouracil and x-ray radiation. Furthermore, RSpo1 significantly reduced the extent of tongue ulceration in mice receiving a single fraction, high dose head-only radiation in a dose-dependent manner. Moreover, combined therapy of RSpo1 and keratinocyte growth factor resulted in complete healing of tongue ulcers in mice subjected to snout-only irradiation. In conclusion, our results demonstrate RSpo1 to be a potent therapeutic agent for oral mucositis by enhancing Basal Layer epithelial regeneration and accelerating mucosal repair through up-regulation of Wnt/β-catenin pathway.
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R-Spondin1 protects mice from chemotherapy or radiation-induced oral mucositis through the canonical Wnt/β-catenin pathway
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Jingsong Zhao, Josephine De Vera, Servando Palencia, Marie WagleAbstract:R-Spondin1 (RSpo1) is a novel secreted protein that augments canonical Wnt/β-catenin signaling. We injected recombinant RSpo1 protein into transgenic Wnt reporter TOPGAL mice and have identified the oral mucosa as a target tissue for RSpo1. Administration of RSpo1 into normal mice triggered nuclear translocation of β-catenin and resulted in increased Basal Layer cellularity, thickened mucosa, and elevated epithelial cell proliferation in tongue. We herein evaluated the therapeutic potential of RSpo1 in treating chemotherapy or radiotherapy-induced oral mucositis in several mouse models. Prophylactic treatment with RSpo1 dose-dependently overcame the reduction of Basal Layer epithelial cellularity, mucosal thickness, and epithelial cell proliferation in tongues of mice exposed to whole-body irradiation. RSpo1 administration also substantially alleviated tongue mucositis in the oral cavity of mice receiving concomitant 5-fluorouracil and x-ray radiation. Furthermore, RSpo1 significantly reduced the extent of tongue ulceration in mice receiving a single fraction, high dose head-only radiation in a dose-dependent manner. Moreover, combined therapy of RSpo1 and keratinocyte growth factor resulted in complete healing of tongue ulcers in mice subjected to snout-only irradiation. In conclusion, our results demonstrate RSpo1 to be a potent therapeutic agent for oral mucositis by enhancing Basal Layer epithelial regeneration and accelerating mucosal repair through up-regulation of Wnt/β-catenin pathway.
Helmut Neumann - One of the best experts on this subject based on the ideXlab platform.
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intercellular space volume is mainly increased in the Basal Layer of esophageal squamous epithelium in patients with gerd
Digestive Diseases and Sciences, 2011Co-Authors: Frank Dombrowski, Doerthe Kuester, Mike Beyer, Klaus Monkemuller, Helmut Neumann, Peter MalfertheinerAbstract:BACKGROUND/AIMS: At present, the dilation of esophageal intercellular spaces (ICS) is considered an early morphologic marker of acid damage in patients with GERD. Nevertheless, previous electron microscopic (EM) studies had focused only on the supraBasal Layer of squamous epithelium or did not nearly specify which Layer of squamous epithelium was studied. Therefore, we aimed to assess the volumetric amount of the ICS in all Layers of SE in patients with GERD. METHODS: In this study, 48 patients were prospectively included (NERD = 18, ERD = 17; Barrett's esophagus = 5, controls = 8). All patients with ERD and NERD had typical reflux symptoms, as assessed by a valid GERD questionnaire. ICS volume was assessed by electron microscopy in the superficial, prickle cell, and Basal Layers of esophageal squamous epithelium using the method of Weibel. RESULTS: ERD was associated with increased ICS volume in the Basal Layer (LA-A, p = 0.038; LA-B, p = 0.005) and prickle cell Layer (LA-A, p = 0.006; LA-B, p = 0.007) as compared to controls. Comparisons between NERD and ERD patients revealed more dilated ICS in the Basal Layer (LA-B, p = 0.007), prickle cell Layer (LA-A, p = 0.008; LA-B, p = 0.001) and superficial Layer (LA-B, p = 0.018) in patients with ERD. CONCLUSIONS: Not only the diameter but also the volume of the ICS is increased in patients with GERD. Furthermore, the dilation of ICS is present in all three Layers of the SE, being more pronounced in the Basal Layer. These findings support the concept that the impairment of the esophagus begins in the deeper parts of the esophageal epithelium.
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intercellular space volume is mainly increased in the Basal Layer of esophageal squamous epithelium in patients with gerd
Digestive Diseases and Sciences, 2011Co-Authors: Frank Dombrowski, Doerthe Kuester, Mike Beyer, Klaus Monkemuller, Helmut Neumann, L C Fry, Peter MalfertheinerAbstract:At present, the dilation of esophageal intercellular spaces (ICS) is considered an early morphologic marker of acid damage in patients with GERD. Nevertheless, previous electron microscopic (EM) studies had focused only on the supraBasal Layer of squamous epithelium or did not nearly specify which Layer of squamous epithelium was studied. Therefore, we aimed to assess the volumetric amount of the ICS in all Layers of SE in patients with GERD. In this study, 48 patients were prospectively included (NERD = 18, ERD = 17; Barrett′s esophagus = 5, controls = 8). All patients with ERD and NERD had typical reflux symptoms, as assessed by a valid GERD questionnaire. ICS volume was assessed by electron microscopy in the superficial, prickle cell, and Basal Layers of esophageal squamous epithelium using the method of Weibel. ERD was associated with increased ICS volume in the Basal Layer (LA-A, p = 0.038; LA-B, p = 0.005) and prickle cell Layer (LA-A, p = 0.006; LA-B, p = 0.007) as compared to controls. Comparisons between NERD and ERD patients revealed more dilated ICS in the Basal Layer (LA-B, p = 0.007), prickle cell Layer (LA-A, p = 0.008; LA-B, p = 0.001) and superficial Layer (LA-B, p = 0.018) in patients with ERD. Not only the diameter but also the volume of the ICS is increased in patients with GERD. Furthermore, the dilation of ICS is present in all three Layers of the SE, being more pronounced in the Basal Layer. These findings support the concept that the impairment of the esophagus begins in the deeper parts of the esophageal epithelium.
Gary M. Halliday - One of the best experts on this subject based on the ideXlab platform.
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It's all about position: the Basal Layer of human epidermis is particularly susceptible to different types of sunlight-induced DNA damage.
The Journal of investigative dermatology, 2012Co-Authors: Gary M. Halliday, Jean CadetAbstract:In this issue, Tewari et al. show that although UVB most effectively causes cyclobutane pyrimidine dimers (CPDs) at the human epidermal surface, UVA-induced CPDs predominate in the Basal Layer. Previous studies found higher accumulation of UVA-induced 8-oxo-7,8-dihydro-2′-deoxyguanosine and mutations in the Basal Layer. Therefore, the epidermal Basal Layer is particularly sensitive to UVA-induced genetic damage and the formation of mutations.
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human 8 oxoguanine dna glycosylase 1 protein and gene are expressed more abundantly in the superficial than Basal Layer of human epidermis
DNA Repair, 2008Co-Authors: Arash Javeri, Xiao Xuan Huang, Francoise Bernerd, Rebecca S Mason, Gary M. HallidayAbstract:Human 8-oxoguanine-DNA glycosylase 1 (hOGG1) repairs 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) which results from oxidation of guanine. Reactive oxygen species (ROS) formed in response to ultraviolet (UV) radiation cause this DNA damage, which is involved in pathological processes such as carcinogenesis and aging. The initiation of skin tumors probably requires penetration of UV to the actively dividing Basal Layer of the epidermis in order for acute damage to become fixed as mutations. Previously, the majority of UVB fingerprint mutations have been found in the upper Layers of human skin tumors, while UVA mutations have been found mostly in the lower Layer. Our aim was to determine whether this localization of UVA-induced DNA damage is related to stratification of the repair-enzyme hOGG1. Anti-hOGG1 immunohistochemical staining of frozen sections of human foreskin, adult buttock skin, and reconstructed human skin samples showed the highest expression of hOGG1 in the superficial epidermal Layer (stratum granulosum). Study of the hOGG1 mRNA expression again showed the highest level in the upper region of the epidermis. This was not regulated by UV irradiation but by the differentiation state of keratinocytes as calcium-induced differentiation increased hOGG1 gene expression. UVA-induced 8-oxo-dG was repaired more rapidly in the upper Layer of human skin compared to the lower Layers. Our results indicate that weaker expression of the nuclear form of hOGG1 enzyme in the Basal cells of the epidermis may lead to a lack of DNA repair in these cells and therefore accumulation of UVA-induced oxidative DNA mutations.
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the Basal Layer in human squamous tumors harbors more uva than uvb fingerprint mutations a role for uva in human skin carcinogenesis
Proceedings of the National Academy of Sciences of the United States of America, 2004Co-Authors: Nita S Agar, Gary M. Halliday, Ross Stc Barnetson, Honnavara N Ananthaswamy, Mark Wheeler, Alexandra M JonesAbstract:We hypothesized that a substantial portion of the mutagenic alterations produced in the Basal Layer of human skin by sunlight are induced by wavelengths in the UVA range. Using laser capture microdissection we examined separately Basal and supraBasal keratinocytes from human skin squamous cell carcinomas and premalignant solar keratosis for both UVA- and UVB-induced adduct formation and signature mutations. We found that UVA fingerprint mutations were detectable in human skin squamous cell carcinomas and solar keratosis, mostly in the Basal germinative Layer, which contrasted with a predominantly supraBasal localization of UVB fingerprint mutations in these lesions. The epidermal Layer bias was confirmed by immunohistochemical analyses with a superficial localization of cyclobutane thymine dimers contrasting with the localization of 8-hydroxy-2′-deoxyguanine adducts to the Basal epithelial Layers. If unrepaired, these adducts may lead to fixed genomic mutations. The Basal location of UVA-rather than UVB-induced DNA damage suggests that longer-wavelength UVR is an important carcinogen in the stem cell compartment of the skin. Given the traditional emphasis on UVB, these results may have profound implications for future public health initiatives for skin cancer prevention.
Peter Malfertheiner - One of the best experts on this subject based on the ideXlab platform.
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intercellular space volume is mainly increased in the Basal Layer of esophageal squamous epithelium in patients with gerd
Digestive Diseases and Sciences, 2011Co-Authors: Frank Dombrowski, Doerthe Kuester, Mike Beyer, Klaus Monkemuller, Helmut Neumann, Peter MalfertheinerAbstract:BACKGROUND/AIMS: At present, the dilation of esophageal intercellular spaces (ICS) is considered an early morphologic marker of acid damage in patients with GERD. Nevertheless, previous electron microscopic (EM) studies had focused only on the supraBasal Layer of squamous epithelium or did not nearly specify which Layer of squamous epithelium was studied. Therefore, we aimed to assess the volumetric amount of the ICS in all Layers of SE in patients with GERD. METHODS: In this study, 48 patients were prospectively included (NERD = 18, ERD = 17; Barrett's esophagus = 5, controls = 8). All patients with ERD and NERD had typical reflux symptoms, as assessed by a valid GERD questionnaire. ICS volume was assessed by electron microscopy in the superficial, prickle cell, and Basal Layers of esophageal squamous epithelium using the method of Weibel. RESULTS: ERD was associated with increased ICS volume in the Basal Layer (LA-A, p = 0.038; LA-B, p = 0.005) and prickle cell Layer (LA-A, p = 0.006; LA-B, p = 0.007) as compared to controls. Comparisons between NERD and ERD patients revealed more dilated ICS in the Basal Layer (LA-B, p = 0.007), prickle cell Layer (LA-A, p = 0.008; LA-B, p = 0.001) and superficial Layer (LA-B, p = 0.018) in patients with ERD. CONCLUSIONS: Not only the diameter but also the volume of the ICS is increased in patients with GERD. Furthermore, the dilation of ICS is present in all three Layers of the SE, being more pronounced in the Basal Layer. These findings support the concept that the impairment of the esophagus begins in the deeper parts of the esophageal epithelium.
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intercellular space volume is mainly increased in the Basal Layer of esophageal squamous epithelium in patients with gerd
Digestive Diseases and Sciences, 2011Co-Authors: Frank Dombrowski, Doerthe Kuester, Mike Beyer, Klaus Monkemuller, Helmut Neumann, L C Fry, Peter MalfertheinerAbstract:At present, the dilation of esophageal intercellular spaces (ICS) is considered an early morphologic marker of acid damage in patients with GERD. Nevertheless, previous electron microscopic (EM) studies had focused only on the supraBasal Layer of squamous epithelium or did not nearly specify which Layer of squamous epithelium was studied. Therefore, we aimed to assess the volumetric amount of the ICS in all Layers of SE in patients with GERD. In this study, 48 patients were prospectively included (NERD = 18, ERD = 17; Barrett′s esophagus = 5, controls = 8). All patients with ERD and NERD had typical reflux symptoms, as assessed by a valid GERD questionnaire. ICS volume was assessed by electron microscopy in the superficial, prickle cell, and Basal Layers of esophageal squamous epithelium using the method of Weibel. ERD was associated with increased ICS volume in the Basal Layer (LA-A, p = 0.038; LA-B, p = 0.005) and prickle cell Layer (LA-A, p = 0.006; LA-B, p = 0.007) as compared to controls. Comparisons between NERD and ERD patients revealed more dilated ICS in the Basal Layer (LA-B, p = 0.007), prickle cell Layer (LA-A, p = 0.008; LA-B, p = 0.001) and superficial Layer (LA-B, p = 0.018) in patients with ERD. Not only the diameter but also the volume of the ICS is increased in patients with GERD. Furthermore, the dilation of ICS is present in all three Layers of the SE, being more pronounced in the Basal Layer. These findings support the concept that the impairment of the esophagus begins in the deeper parts of the esophageal epithelium.
