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Annals of the New York Academy of... Oct 2017Epithelial cells constitute a physical barrier that aids in protecting the host from microbial pathogens. Polarized epithelial cells contain distinct apical and... (Review)
Review
Epithelial cells constitute a physical barrier that aids in protecting the host from microbial pathogens. Polarized epithelial cells contain distinct apical and basolateral membrane domains separated by intercellular junctions, including tight junctions (TJs), which contribute to the maintenance of apical-basal polarity. Polarity complexes also contribute to the establishment of TJ formation. Several pathogens perturb epithelial TJ barrier function and structure in addition to causing a loss of apical-basal polarity. Here, we review the impact of pathogenic bacteria on the disruption of cell-cell junctions and epithelial polarity.
Topics: Animals; Cell Polarity; Epithelial Cells; Escherichia coli; Humans; Membrane Proteins; Tight Junctions
PubMed: 28628193
DOI: 10.1111/nyas.13388 -
Biology Open Apr 2023Under homeostatic conditions, epithelial cells remain non-migratory. However, during embryonic development and pathological conditions, they become migratory. The...
Under homeostatic conditions, epithelial cells remain non-migratory. However, during embryonic development and pathological conditions, they become migratory. The mechanism underlying the transition of the epithelial layer between non-migratory and migratory phases is a fundamental question in biology. Using well-differentiated primary human bronchial epithelial cells that form a pseudostratified epithelium, we have previously identified that a confluent epithelial layer can transition from a non-migratory to migratory phase through an unjamming transition (UJT). We previously defined collective cellular migration and apical cell elongation as hallmarks of UJT. However, other cell-type-specific changes have not been previously studied in the pseudostratified airway epithelium, which consists of multiple cell types. Here, we focused on the quantifying morphological changes in basal stem cells during the UJT. Our data demonstrate that during the UJT, airway basal stem cells elongated and enlarged, and their stress fibers elongated and aligned. These morphological changes observed in basal stem cells correlated to the previously defined hallmarks of the UJT. Moreover, basal cell and stress fiber elongation were observed prior to apical cell elongation. Together, these morphological changes indicate that basal stem cells in pseudostratified airway epithelium are actively remodeling, presumably through accumulation of stress fibers during the UJT.
Topics: Humans; Stress Fibers; Epithelium; Epithelial Cells; Cell Proliferation; Stem Cells
PubMed: 37014330
DOI: 10.1242/bio.059727 -
Traffic (Copenhagen, Denmark) Dec 2020Radial glial cells (RGCs) are progenitors of the cerebral cortex which produce both neurons and glia during development. Given their central role in development, RGC... (Review)
Review
Radial glial cells (RGCs) are progenitors of the cerebral cortex which produce both neurons and glia during development. Given their central role in development, RGC dysfunction can result in diverse neurodevelopmental disorders. RGCs have an elongated bipolar morphology that spans the entire radial width of the cortex and ends in basal endfeet connected to the pia. The basal process and endfeet are important for proper guidance of migrating neurons and are implicated in signaling. However, endfeet must function at a great distance from the cell body. This spatial separation suggests a role for local gene regulation in endfeet. Endfeet contain a local transcriptome enriched for cytoskeletal and signaling factors. These localized mRNAs are actively transported from the cell body and can be locally translated in endfeet. Yet, studies of local gene regulation in RGC endfeet are still in their infancy. Here, we draw comparisons of RGCs with foundational work in anatomically and phylogenetically related cell types, neurons and astrocytes. Our review highlights a striking overlap in the types of RNAs localized, as well as principles of local translation between these three cell types. Thus, studies in neurons, astrocytes and RGCs can mutually inform an understanding of RNA localization across the nervous system.
Topics: Astrocytes; Cerebral Cortex; Ependymoglial Cells; Neuroglia; Neurons
PubMed: 33058331
DOI: 10.1111/tra.12769 -
Proceedings of the National Academy of... Jul 2020Fluctuation in signal transduction pathways is frequently observed during mammalian development. However, its role in regulating stem cells has not been explored. Here...
Fluctuation in signal transduction pathways is frequently observed during mammalian development. However, its role in regulating stem cells has not been explored. Here we tracked spatiotemporal ERK MAPK dynamics in human epidermal stem cells. While stem cells and differentiated cells were distinguished by high and low stable basal ERK activity, respectively, we also found cells with pulsatile ERK activity. Transitions from Basal-Pulse (stem) to Basal-Pulse, Basal-Pulse, and Basal-Pulse (differentiated) cells occurred in expanding keratinocyte colonies and in response to differentiation stimuli. Pharmacological inhibition of ERK induced differentiation only when cells were in the Basal-Pulse state. Basal ERK activity and pulses were differentially regulated by DUSP10 and DUSP6, leading us to speculate that DUSP6-mediated ERK pulse down-regulation promotes initiation of differentiation, whereas DUSP10-mediated down-regulation of mean ERK activity promotes and stabilizes postcommitment differentiation. Levels of MAPK1/MAPK3 transcripts correlated with DUSP6 and DUSP10 transcripts in individual cells, suggesting that ERK activity is negatively regulated by transcriptional and posttranslational mechanisms. When cells were cultured on a topography that mimics the epidermal-dermal interface, spatial segregation of mean ERK activity and pulses was observed. In vivo imaging of mouse epidermis revealed a patterned distribution of basal cells with pulsatile ERK activity, and down-regulation was linked to the onset of differentiation. Our findings demonstrate that ERK MAPK signal fluctuations link kinase activity to stem cell dynamics.
Topics: Animals; Cell Culture Techniques; Cell Differentiation; Cell Proliferation; Enzyme Activation; Epidermal Cells; Extracellular Signal-Regulated MAP Kinases; Keratinocytes; Mammals; Mice; Phosphoprotein Phosphatases; Signal Transduction; Stem Cells
PubMed: 32651268
DOI: 10.1073/pnas.2006965117 -
Reproduction, Fertility, and Development Oct 2014Basal cells are present in the columnar pseudostratified epithelium covering the epididymis of all mammalian species, which regulates the microenvironment where the... (Review)
Review
Basal cells are present in the columnar pseudostratified epithelium covering the epididymis of all mammalian species, which regulates the microenvironment where the functionally incompetent germ cells produced by the testis are matured and stored. Striking novelties have come from investigations on epididymal basal cells in the past 30-40 years. In addition to an earlier hypothesised scavenger role for basal cells, linked to their proven extratubular origin and the expression of macrophage antigens, basal cells have been shown to be involved in cell-cell cross-talk, as well as functioning as luminal sensors to regulate the activity of principal and clear cells. Involvement of basal cells in the regulation of electrolyte and water transport by principal cells was hypothesised. This control is suggested to be mediated by the local formation of prostaglandins. Members of the aquaporin (AQP) and/or aquaglyceroporin family (AQP3, AQP7 and AQP8) are also specifically expressed in the rat epididymal basal cells. Transport of glycerol and glycerylphosphorylcholine from the epithelium of the epididymis to the lumen in relation to sperm maturation may be mediated by AQP. Most probably basal cells collaborate to the building up of the blood-epididymis barrier through cell adhesion molecules, implying an involvement in immune control exerted towards sperm cells, which are foreigners in the environment in which they were produced.
Topics: Animals; Aquaporins; Cell Communication; Cell Differentiation; Cell Lineage; Epididymis; Epithelial Cells; Glycerol; Glycerylphosphorylcholine; Male; Prostaglandins; Signal Transduction; Spermatozoa
PubMed: 24138802
DOI: 10.1071/RD13301 -
Cell Stem Cell Mar 2021Basal stem cells fuel development, homeostasis, and regeneration of the epidermis. The proliferation and fate decisions of these cells are highly regulated by their...
Basal stem cells fuel development, homeostasis, and regeneration of the epidermis. The proliferation and fate decisions of these cells are highly regulated by their microenvironment, including the basement membrane and underlying mesenchymal cells. Basal progenitors give rise to differentiated progeny that generate the epidermal barrier. Here, we present data that differentiated progeny also regulate the proliferation, differentiation, and migration of basal progenitor cells. Using two distinct mouse lines, we found that increasing contractility of differentiated cells resulted in non-cell-autonomous hyperproliferation of stem cells and prevented their commitment to a hair follicle lineage. This increased contractility also impaired movement of basal progenitors during hair placode morphogenesis and diminished migration of melanoblasts. These data suggest that intra-tissue tension regulates stem cell proliferation, fate decisions, and migration and that differentiated epidermal keratinocytes are a component of the stem cell niche that regulates development and homeostasis of the skin.
Topics: Animals; Cell Differentiation; Cell Proliferation; Epidermal Cells; Epidermis; Hair Follicle; Keratinocytes; Mice; Stem Cells
PubMed: 33264636
DOI: 10.1016/j.stem.2020.11.002 -
Developmental Cell Dec 2023The extrahepatic branches of the biliary tree have glands that connect to the surface epithelium through narrow pits. The duct epithelia undergo homeostatic renewal, yet...
The extrahepatic branches of the biliary tree have glands that connect to the surface epithelium through narrow pits. The duct epithelia undergo homeostatic renewal, yet the identity and multiplicity of cells that maintain this tissue is unknown. Using marker-free and targeted clonal fate mapping in mice, we provide evidence that the extrahepatic bile duct is compartmentalized. Pit cholangiocytes of extramural glands renewed the surface epithelium, whereas basally oriented cholangiocytes maintained the gland itself. In contrast, basally positioned cholangiocytes replenished the surface epithelium in mural glands. Single-cell sequencing identified genes enriched in the base and surface epithelial populations, with trajectory analysis showing graded gene expression between these compartments. Epithelia were plastic, changing cellular identity upon fasting and refeeding. Gain of canonical Wnt signaling caused basal cell expansion, gastric chief cell marker expression, and a decrease in surface epithelial markers. Our results identify the cellular hierarchy governing extrahepatic biliary epithelial renewal.
Topics: Animals; Mice; Biliary Tract; Bile Ducts, Extrahepatic; Epithelium; Epithelial Cells; Cell Proliferation
PubMed: 37909044
DOI: 10.1016/j.devcel.2023.10.004 -
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 -
Nature Reviews. Molecular Cell Biology Apr 2014Epithelial cells require apical-basal plasma membrane polarity to carry out crucial vectorial transport functions and cytoplasmic polarity to generate different cell... (Review)
Review
Epithelial cells require apical-basal plasma membrane polarity to carry out crucial vectorial transport functions and cytoplasmic polarity to generate different cell progenies for tissue morphogenesis. The establishment and maintenance of a polarized epithelial cell with apical, basolateral and ciliary surface domains is guided by an epithelial polarity programme (EPP) that is controlled by a network of protein and lipid regulators. The EPP is organized in response to extracellular cues and is executed through the establishment of an apical-basal axis, intercellular junctions, epithelial-specific cytoskeletal rearrangements and a polarized trafficking machinery. Recent studies have provided insight into the interactions of the EPP with the polarized trafficking machinery and how these regulate epithelial polarization and depolarization.
Topics: Animals; Cell Membrane; Cell Polarity; Epithelial Cells; Humans; Intercellular Junctions; Morphogenesis; Signal Transduction
PubMed: 24651541
DOI: 10.1038/nrm3775 -
Proceedings of the National Academy of... Jun 2022As a sedentary epithelium turns motile during wound healing, morphogenesis, and metastasis, the Golgi apparatus moves from an apical position, above the nucleus, to a...
As a sedentary epithelium turns motile during wound healing, morphogenesis, and metastasis, the Golgi apparatus moves from an apical position, above the nucleus, to a basal position. This apical-to-basal repositioning of Golgi is critical for epithelial cell migration. Yet the molecular mechanism underlying it remains elusive, although microtubules are believed to play a role. Using live-cell and super-resolution imaging, we show that at the onset of collective migration of epithelial cells, Golgi stacks get dispersed to create an unpolarized transitional structure, and surprisingly, this dispersal process depends not on microtubules but on actin cytoskeleton. Golgi-actin interaction involves Arp2/3-driven actin projections emanating from the actin cortex, and a Golgi-localized actin elongation factor, MENA. While in sedentary epithelial cells, actin projections intermittently interact with the apically located Golgi, and the frequency of this event increases before the dispersion of Golgi stacks, at the onset of cell migration. Preventing Golgi-actin interaction with MENA-mutants eliminates Golgi dispersion and reduces the persistence of cell migration. Taken together, we show a process of actin-driven Golgi dispersion that is mechanistically different from the well-known Golgi apparatus fragmentation during mitosis and is essential for collective migration of epithelial cells.
Topics: Actin Cytoskeleton; Actins; Animals; Cell Movement; Dogs; Epithelial Cells; Golgi Apparatus; Madin Darby Canine Kidney Cells; Microfilament Proteins; Microtubules
PubMed: 35749357
DOI: 10.1073/pnas.2204808119