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Facial Plastic Surgery Clinics of North... Aug 2017Skin is composed of the epidermis, dermis, and adnexal structures. The epidermis is composed of 4 layers-the stratums basale, spinosum, granulosum, and corneum. The... (Review)
Review
Skin is composed of the epidermis, dermis, and adnexal structures. The epidermis is composed of 4 layers-the stratums basale, spinosum, granulosum, and corneum. The dermis is divided into a superficial papillary dermis and deeper reticular dermis. Collagen and elastin within the reticular dermis are responsible for skin tensile strength and elasticity, respectively. The 2 most common kinds of nonmelanoma skin cancers are basal cell and squamous cell carcinoma. Both are caused by a host of environmental and genetic factors, although UV light exposure is the single greatest predisposing factor.
Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Dermis; Epidermal Cells; Epidermis; Gene-Environment Interaction; Humans; Skin; Skin Neoplasms
PubMed: 28676156
DOI: 10.1016/j.fsc.2017.03.001 -
Current Allergy and Asthma Reports Nov 2019To describe inherited and acquired genetic variants and clinical entities associated with increased basal serum tryptase (BST), distinguish these levels from those which... (Review)
Review
PURPOSE OF REVIEW
To describe inherited and acquired genetic variants and clinical entities associated with increased basal serum tryptase (BST), distinguish these levels from those which acutely rise due to mast cell activation, and finally to characterize the association between chronically elevated basal serum tryptase and episodic mast cell activation.
RECENT FINDINGS
Hereditary alpha-tryptasemia is a commonly inherited genetic cause for basally elevated serum tryptase and explains elevated BST in many individuals who do not have evidence of clonal myeloid or mast cell disease. When clonal myeloid disease is present, BST may be elevated and can be a biomarker of a number of disparate disorders of the myeloid compartment. Elevated BST is most commonly caused by hereditary alpha tryptasemia but may also be indicative of clonal myeloid disease. Clinical reports suggest that elevated BST is associated with increased risk for more severe systemic allergic reactions to a number of eliciting agents and exposures. Additional studies are needed to determine the role that inherited or acquired genetic variants associated with elevated BST and clonal or non-clonal myeloid diseases may play in these reactions.
Topics: Genetic Diseases, Inborn; Genetic Variation; Humans; Mast Cells; Tryptases
PubMed: 31776770
DOI: 10.1007/s11882-019-0887-x -
Nature Reviews. Cancer Jul 2014Metastasis is the leading cause of cancer-related deaths, but it is unclear how cancer cells escape their primary sites in epithelia and disseminate to other sites in... (Review)
Review
Metastasis is the leading cause of cancer-related deaths, but it is unclear how cancer cells escape their primary sites in epithelia and disseminate to other sites in the body. One emerging possibility is that transformed epithelial cells could invade the underlying tissue by a process called cell extrusion, which epithelia use to remove cells without disrupting their barrier function. Typically, during normal cell turnover, live cells extrude apically from the epithelium into the lumen and later die by anoikis; however, several oncogenic mutations shift cell extrusion basally, towards the tissue that the epithelium encases. Tumour cells with high levels of survival and motility signals could use basal extrusion to escape from the tissue and migrate to other sites within the body.
Topics: Cell Movement; Epithelial Cells; Humans; Neoplasm Invasiveness; Neoplasms
PubMed: 24943812
DOI: 10.1038/nrc3767 -
Methods in Molecular Biology (Clifton,... 2022In this chapter, an efficient feeder-free protocol of differentiating human pluripotent stem cells (hPSCs) toward the epidermal lineage to generate induced epidermal...
In this chapter, an efficient feeder-free protocol of differentiating human pluripotent stem cells (hPSCs) toward the epidermal lineage to generate induced epidermal keratinocytes (iKCs) is described. The iKCs are able to terminally differentiate supra-basally. This hPSC-to-iKC differentiation can serve as a useful model to study epidermal development and disease as well as for therapeutic applications.
Topics: Cell Differentiation; Cell Line; Epithelial Cells; Humans; Induced Pluripotent Stem Cells; Pluripotent Stem Cells
PubMed: 32833130
DOI: 10.1007/7651_2020_301 -
Proceedings of the National Academy of... Dec 2013Here, using further optimized 3D culture that allows highly selective induction and long-term growth of human ES cell (hESC)-derived cortical neuroepithelium, we...
Here, using further optimized 3D culture that allows highly selective induction and long-term growth of human ES cell (hESC)-derived cortical neuroepithelium, we demonstrate unique aspects of self-organization in human neocorticogenesis. Self-organized cortical tissue spontaneously forms a polarity along the dorsocaudal-ventrorostral axis and undergoes region-specific rolling morphogenesis that generates a semispherical structure. The neuroepithelium self-forms a multilayered structure including three neuronal zones (subplate, cortical plate, and Cajal-Retzius cell zones) and three progenitor zones (ventricular, subventricular, and intermediate zones) in the same apical-basal order as seen in the human fetal cortex in the early second trimester. In the cortical plate, late-born neurons tend to localize more basally to early-born neurons, consistent with the inside-out pattern seen in vivo. Furthermore, the outer subventricular zone contains basal progenitors that share characteristics with outer radial glia abundantly found in the human, but not mouse, fetal brain. Thus, human neocorticogenesis involves intrinsic programs that enable the emergence of complex neocortical features.
Topics: Amides; Cell Culture Techniques; Cell Polarity; Collagen; Drug Combinations; Embryonic Stem Cells; Humans; Laminin; Neocortex; Neuroglia; Organogenesis; Proteoglycans; Pyridines; Species Specificity
PubMed: 24277810
DOI: 10.1073/pnas.1315710110 -
Biochemical and Biophysical Research... Mar 2021Oncogenic transformation enables cells to behave differently from their neighboring normal cells. Both cancer and normal cells recognize each other, often promoting the...
Oncogenic transformation enables cells to behave differently from their neighboring normal cells. Both cancer and normal cells recognize each other, often promoting the extrusion of the former from the epithelial cell layer. Here, we show that RasV12-transformed normal rat kidney 52E (NRK-52E) cells are extruded towards the basal side of the surrounding normal cells, which is concomitant with enhanced motility. The active migration of the basally extruded RasV12 cells is observed when surrounded by normal cells, indicating a non-cell-autonomous mechanism. Furthermore, specific inhibitor treatment and knockdown experiments elucidate the roles of PI3K and myosin IIA in the basal extrusion of Ras cells. Our findings reveal a new aspect of cancer cell invasion mediated by functional interactions with surrounding non-transformed cells.
Topics: Amino Acid Sequence; Animals; Cell Movement; Cells, Cultured; Dogs; Humans; Mutation; Neoplasms; Nonmuscle Myosin Type IIA; Oncogene Protein p21(ras); Phosphatidylinositol 3-Kinases; Rats; Signal Transduction; Valine
PubMed: 33503542
DOI: 10.1016/j.bbrc.2021.01.031 -
Cell Stem Cell Nov 2008Here, we demonstrate self-organized formation of apico-basally polarized cortical tissues from ESCs using an efficient three-dimensional aggregation culture (SFEBq...
Here, we demonstrate self-organized formation of apico-basally polarized cortical tissues from ESCs using an efficient three-dimensional aggregation culture (SFEBq culture). The generated cortical neurons are functional, transplantable, and capable of forming proper long-range connections in vivo and in vitro. The regional identity of the generated pallial tissues can be selectively controlled (into olfactory bulb, rostral and caudal cortices, hem, and choroid plexus) by secreted patterning factors such as Fgf, Wnt, and BMP. In addition, the in vivo-mimicking birth order of distinct cortical neurons permits the selective generation of particular layer-specific neurons by timed induction of cell-cycle exit. Importantly, cortical tissues generated from mouse and human ESCs form a self-organized structure that includes four distinct zones (ventricular, early and late cortical-plate, and Cajal-Retzius cell zones) along the apico-basal direction. Thus, spatial and temporal aspects of early corticogenesis are recapitulated and can be manipulated in this ESC culture.
Topics: Animals; Antigens, Differentiation; Body Patterning; Bone Morphogenetic Protein 4; Cell Cycle; Cell Differentiation; Cerebral Cortex; Embryonic Stem Cells; Fibroblast Growth Factor 8; Gene Expression Regulation, Developmental; Homeostasis; Humans; Immunohistochemistry; Mice; Neurons; Signal Transduction; Tissue Culture Techniques; Wnt Proteins; Wnt3 Protein
PubMed: 18983967
DOI: 10.1016/j.stem.2008.09.002 -
Proceedings of the National Academy of... Nov 2019Metastasis is the main cause of cancer-related deaths. How a single oncogenic cell evolves within highly organized epithelium is still unknown. Here, we found that the...
Metastasis is the main cause of cancer-related deaths. How a single oncogenic cell evolves within highly organized epithelium is still unknown. Here, we found that the overexpression of the protein kinase atypical protein kinase C ι (aPKCi), an oncogene, triggers basally oriented epithelial cell extrusion in vivo as a potential mechanism for early breast tumor cell invasion. We found that cell segregation is the first step required for basal extrusion of luminal cells and identify aPKCi and vinculin as regulators of cell segregation. We propose that asymmetric vinculin levels at the junction between normal and aPKCi cells trigger an increase in tension at these cell junctions. Moreover, we show that aPKCi cells acquire promigratory features, including increased vinculin levels and vinculin dynamics at the cell-substratum contacts. Overall, this study shows that a balance between cell contractility and cell-cell adhesion is crucial for promoting basally oriented cell extrusion, a mechanism for early breast cancer cell invasion.
Topics: Breast Neoplasms; Cell Adhesion; Cell Line, Tumor; Cell Separation; Humans; Intercellular Junctions; Isoenzymes; Neoplasm Invasiveness; Protein Kinase C; Vinculin
PubMed: 31699818
DOI: 10.1073/pnas.1906779116 -
Acta Dermato-venereologica Jan 2019Deregulated Hedgehog signalling is a driver of basal cell carcinomas. One effector of the Hedgehog pathway is n-MYC. c/n-MYC proteins, NAMPT and DBC1 are linked to SIRT1...
Deregulated Hedgehog signalling is a driver of basal cell carcinomas. One effector of the Hedgehog pathway is n-MYC. c/n-MYC proteins, NAMPT and DBC1 are linked to SIRT1 in a positive feedback loop that may contribute to tumorigenesis of basal cell carcinoma. In 5 basal cell carcinoma types immunohistochemistry revealed n-MYC, NAMPT and SIRT1 expression. DBC1 was homogenously expressed in all epithelial cells. NAMPT, SIRT1 and c-MYC were expressed in the stratum basale of human and murine skin. In hair follicles NAMPT and SIRT1 were expressed together with c-MYC and n-MYC, except for the matrix, where n-MYC was strongly positive, but c-MYC expression was absent. Therefore, a common pathway connecting n-MYC, NAMPT and SIRT1 may be active in basal cell carcinomas and in their cells of origin. This pathway may contribute to the development of basal cell carcinomas. Targeting factors in the feedback loop may offer novel therapeutic options.
Topics: Adaptor Proteins, Signal Transducing; Animals; Biomarkers, Tumor; Biopsy; Carcinoma, Basal Cell; Cell Cycle Proteins; Cytokines; Humans; Immunohistochemistry; Mice; Mice, Inbred C57BL; Neoplastic Stem Cells; Nerve Tissue Proteins; Nicotinamide Phosphoribosyltransferase; Proto-Oncogene Proteins c-myc; Sirtuin 1; Skin Neoplasms
PubMed: 30182136
DOI: 10.2340/00015555-3031 -
Current Opinion in Cell Biology Oct 2018Cell extrusion drives most epithelial cell death while maintaining a functional epithelial barrier. To extrude, a cell produces a lipid signal that triggers the... (Review)
Review
Cell extrusion drives most epithelial cell death while maintaining a functional epithelial barrier. To extrude, a cell produces a lipid signal that triggers the neighboring cells to reorganize actin and myosin basally to squeeze the extruding cell out apically from the barrier. More studies continue to reveal other signals and mechanisms controlling apical extrusion. New developmental studies are uncovering mechanisms controlling basal extrusion, or ingression, which occurs when apical extrusion is defective or during de-differentiation in development. Here, we review recent advances in epithelial extrusion, focusing particularly on forces exerted upon extruding cells and their various later fates ranging from cell death, normal development, and cancer.
Topics: Actins; Animals; Biomechanical Phenomena; Disease; Epithelial Cells; Humans; Myosins; Nervous System
PubMed: 29727745
DOI: 10.1016/j.ceb.2018.04.007