Stem Cells and Rat Liver Carcinogenesis: Contributions of Confocal and Electron Microscopy

Microscopic analysis in combination with cytochemistry and immunocytochemistry has revealed the presence of four cell types not previously described in the portal area and parenchyma of the liver from an experimental rodent hepatocarcinogenic rat model. Within the intrahepatic bile ductules, which proliferate after administration of chemical carcinogens and partial hepatectomy, small, undifferentiated nonpolarized, nonepithelial cells with a blast-like phenotype and polarized epithelial cells different from the polarized epithelial cells that typically line the walls of the bile ductules were found. In the connective tissue stroma surrounding the bile ductules, nonpolarized epithelial cells with hepatocyte phenotype were found. In the parenchyma, subpopulations of bile ductule epithelial cells that established ATPase-positive bile canalicular structures, including the formation of desmosomes and tight junctions, with parenchymal hepatocytes within the hepatic lobule were found. These observations raise the following questions in this model. Are there undifferentiated progenitor cells with stem cell-like properties within bile ductules? What are the interrelations of the newly described cell types with each other, with parenchymal hepatocytes, with preneoplastic nodules, and with hepatomas? Do the heterogeneous cell types within the bile ductules, in the surrounding connective tissue, and within the hepatic cords represent intermediate stages of single or multiple cell lineage pathways leading to hepatocyte differentiation, liver regeneration, and/or preneoplastic nodule formation?

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The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and Cancer

Cells ◽

10.3390/cells10051065 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1065

Author(s):

Armando Rubio-Ramos ◽

Leticia Labat-de-Hoz ◽

Isabel Correas ◽

Miguel A. Alonso

Keyword(s):

Epithelial Cells ◽

Large Body ◽

Original Description ◽

Cell Types ◽

Future Research ◽

Transmembrane Segments ◽

Epsilon Toxin ◽

Proteolipid Proteins ◽

Polarized Epithelial Cells

The MAL gene encodes a 17-kDa protein containing four putative transmembrane segments whose expression is restricted to human T cells, polarized epithelial cells and myelin-forming cells. The MAL protein has two unusual biochemical features. First, it has lipid-like properties that qualify it as a member of the group of proteolipid proteins. Second, it partitions selectively into detergent-insoluble membranes, which are known to be enriched in condensed cell membranes, consistent with MAL being distributed in highly ordered membranes in the cell. Since its original description more than thirty years ago, a large body of evidence has accumulated supporting a role of MAL in specialized membranes in all the cell types in which it is expressed. Here, we review the structure, expression and biochemical characteristics of MAL, and discuss the association of MAL with raft membranes and the function of MAL in polarized epithelial cells, T lymphocytes, and myelin-forming cells. The evidence that MAL is a putative receptor of the epsilon toxin of Clostridium perfringens, the expression of MAL in lymphomas, the hypermethylation of the MAL gene and subsequent loss of MAL expression in carcinomas are also presented. We propose a model of MAL as the organizer of specialized condensed membranes to make them functional, discuss the role of MAL as a tumor suppressor in carcinomas, consider its potential use as a cancer biomarker, and summarize the directions for future research.

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Cell lineage in marine nematode Enoplus brevis

Development ◽

10.1242/dev.125.1.143 ◽

1998 ◽

Vol 125 (1) ◽

pp. 143-150

Author(s):

D.A. Voronov ◽

Y.V. Panchin

Keyword(s):

Fluorescent Dyes ◽

Cell Lineage ◽

Cell Types ◽

Ventral Side ◽

Marine Nematode ◽

Cell Stage ◽

Cell Embryo ◽

Multiple Cell ◽

Nerve Muscle ◽

Nematode Development

Early cleavages of the marine nematode Enoplus brevis are symmetrical and occur in synchrony. At the 2- to 16-cell stages, blastomeres are indistinguishable. The progeny of blastomeres was investigated by intracellular injections of fluorescent dyes and horse radish peroxidase. One blastomere of the 2-cell embryo gives rise to a compact group of cells occupying about half of an embryo. The border between labeled and unlabeled cells differs in each embryo dividing it to anterior-posterior, left-right or intermediate parts. At the 8-cell stage, one blastomere gives rise to only endoderm, whereas the other blastomeres produce progeny that form multiple cell types, including nerve, muscle and hypoderm cells, in various proportions. Thus the fates of the blastomeres of early E. brevis embryos, with the exception of the endoderm precursor, are not determined. The process of gastrulation in E. brevis is very similar to that in Caenorhabditis elegans and other nematodes. At the beginning of gastrulation, the 2-celled endoderm precursor lies on the surface of embryo and then sinks inwards. After labeling of cells on the ventral side (near endoderm precursor) at the beginning of gastrulation, their progeny differentiate predominantly into body muscles or pharyngeal cells of the first stage larva. Cells that are located more laterally give rise mainly to neurons. The dorsal blastomeres differentiated principally into hypoderm cells. Our study suggests that a precise cell lineage is not a necessary attribute of nematode development.

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Disruption of Lipid Rafts Interferes with the Interaction ofToxoplasma gondiiwith Macrophages and Epithelial Cells

BioMed Research International ◽

10.1155/2014/687835 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Karla Dias Cruz ◽

Thayana Araújo Cruz ◽

Gabriela Veras de Moraes ◽

Tatiana Christina Paredes-Santos ◽

Marcia Attias ◽

...

Keyword(s):

Epithelial Cells ◽

Host Cell ◽

Lipid Rafts ◽

Tyrosine Kinases ◽

Plasma Membranes ◽

Animal Cell ◽

Cell Lineage ◽

Cell Types ◽

Peritoneal Macrophages ◽

Membrane Microdomains

The intracellular parasiteToxoplasma gondiican penetrate any warm-blooded animal cell. Conserved molecular assemblies of host cell plasma membranes should be involved in the parasite-host cell recognition. Lipid rafts are well-conserved membrane microdomains that contain high concentrations of cholesterol, sphingolipids, glycosylphosphatidylinositol, GPI-anchored proteins, and dually acylated proteins such as members of the Src family of tyrosine kinases. Disturbing lipid rafts of mouse peritoneal macrophages and epithelial cells of the lineage LLC-MK2 with methyl-beta cyclodextrin (MβCD) and filipin, which interfere with cholesterol or lidocaine, significantly inhibited internalization ofT. gondiiin both cell types, although adhesion remained unaffected in macrophages and decreased only in LLC-MK2 cells. Scanning and transmission electron microscopy confirmed these observations. Results are discussed in terms of the original role of macrophages as professional phagocytes versus the LLC-MK2 cell lineage originated from kidney epithelial cells.

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Keratinocyte Function in Normal and Diabetic Wounds and Modulation by FOXO1

Journal of Diabetes Research ◽

10.1155/2020/3714704 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Yulan Wang ◽

Dana T. Graves

Keyword(s):

Growth Factor ◽

Connective Tissue ◽

Transforming Growth Factor ◽

Negative Impact ◽

Healing Process ◽

Transforming Growth Factor Β ◽

Cell Types ◽

Tissue Growth ◽

Complex Interactions ◽

Multiple Cell

Diabetes has a significant and negative impact on wound healing, which involves complex interactions between multiple cell types. Keratinocytes play a crucial role in the healing process by rapidly covering dermal and mucosal wound surfaces to reestablish an epithelial barrier with the outside environment. Keratinocytes produce multiple factors to promote reepithelialization and produce factors that enhance connective tissue repair through the elaboration of mediators that stimulate angiogenesis and production of connective tissue matrix. Among the factors that keratinocytes produce to aid healing are transforming growth factor-β (TGF-β), vascular endothelial growth factor-A (VEGF-A), connective tissue growth factor (CTGF), and antioxidants. In a diabetic environment, this program is disrupted, and keratinocytes fail to produce growth factors and instead switch to a program that is detrimental to healing. Changes in keratinocyte behavior have been linked to high glucose and advanced glycation end products that alter the activities of the transcription factor, FOXO1. This review examines reepithelialization and factors produced by keratinocytes that upregulate connective tissue healing and angiogenesis and how they are altered by diabetes.

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174 Processing of APP in polarized epithelial cells and neurons: relationships among cell types

Neurobiology of Aging ◽

10.1016/s0197-4580(96)80176-x ◽

1996 ◽

Vol 17 (4) ◽

pp. S44-S45

Author(s):

B. De Strooper ◽

D. Moechars ◽

P. Tienari ◽

M. Simons ◽

K. Beyreuther ◽

...

Keyword(s):

Epithelial Cells ◽

Cell Types ◽

Polarized Epithelial Cells

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Cell Lineage Tracing and Cellular Diversity in Humans

Annual Review of Genomics and Human Genetics ◽

10.1146/annurev-genom-083118-015241 ◽

2020 ◽

Vol 21 (1) ◽

pp. 101-116 ◽

Cited By ~ 1

Author(s):

Alexej Abyzov ◽

Flora M. Vaccarino

Keyword(s):

Methylation Status ◽

Cell Lineage ◽

Cell Types ◽

Lineage Tracing ◽

Data Types ◽

Advantages And Disadvantages ◽

Embryonic And Fetal Development ◽

Distinct Lineage ◽

Multiple Cell ◽

Natural Mutation

Tracing cell lineages is fundamental for understanding the rules governing development in multicellular organisms and delineating complex biological processes involving the differentiation of multiple cell types with distinct lineage hierarchies. In humans, experimental lineage tracing is unethical, and one has to rely on natural-mutation markers that are created within cells as they proliferate and age. Recent studies have demonstrated that it is now possible to trace lineages in normal, noncancerous cells with a variety of data types using natural variations in the nuclear and mitochondrial DNA as well as variations in DNA methylation status. It is also apparent that the scientific community is on the verge of being able to make a comprehensive and detailed cell lineage map of human embryonic and fetal development. In this review, we discuss the advantages and disadvantages of different approaches and markers for lineage tracing. We also describe the general conceptual design for how to derive a lineage map for humans.

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Characterization of a Human In Vitro Intestinal Model for the Hazard Assessment of Nanomaterials Used in Cancer Immunotherapy

Applied Sciences ◽

10.3390/app11052113 ◽

2021 ◽

Vol 11 (5) ◽

pp. 2113

Author(s):

Matthew Gibb ◽

Sahar H. Pradhan ◽

Marina R. Mulenos ◽

Henry Lujan ◽

James Liu ◽

...

Keyword(s):

Epithelial Cells ◽

Microscopic Analysis ◽

Cell Types ◽

Seeding Density ◽

Animal Testing ◽

Barrier Integrity ◽

International Agencies ◽

Culture Models ◽

And Function

There is momentum in biomedical research to improve the structure and function of in vitro intestinal models that better represent human biology. To build a more comprehensive model, three human cell-types were co-cultured and characterized: i.e., HT29-MTX (intestinal mucous-producing goblet cells), Caco-2 (colon epithelial cells), and Raji B (lymphocytes). Raji B cells transformed a subpopulation of Caco-2 epithelial cells into phagocytic and transcytotic immune-supporting microfold cells (M-cells). A suite of bioassays was implemented to investigate steady-state barrier integrity and cellular communication. The model demonstrated a potentiating effect in metabolism and pro-inflammatory markers. Barrier integrity and cell seeding density seem to play a role in the reliability of endpoint readouts. Microscopic analysis elucidated the importance of multi-cell biomimicry. The data show that monocultures do not have the same characteristics inherent to triple cell culture models. Multiple cell types in an in vitro model produce a better representation of an intact organ and aid in the ability to assess immunomodulatory effects of nanomaterials designed for cancer theranostics after ingestion. As many national and international agencies have stressed, there is a critical need to improve alternative-to-animal strategies for pharmaceuticals in an effort to reduce animal testing.

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Epithelial Cell Lineage and Signaling in Murine Salivary Glands

Journal of Dental Research ◽

10.1177/0022034519864592 ◽

2019 ◽

Vol 98 (11) ◽

pp. 1186-1194 ◽

Cited By ~ 4

Author(s):

M.H. Aure ◽

J.M. Symonds ◽

J.W. Mays ◽

M.P. Hoffman

Keyword(s):

Salivary Gland ◽

Epithelial Cells ◽

Cell Fate ◽

Cell Lineage ◽

Cell Types ◽

Lineage Tracing ◽

Genetic Lineage ◽

Recent Advances ◽

Epithelial Development ◽

Gland Development

Maintaining salivary gland function is critical for oral health. Loss of saliva is a common side effect of therapeutic irradiation for head and neck cancer or autoimmune diseases such as Sjögren’s syndrome. There is no curative treatment, and current strategies proposed for functional regeneration include gene therapy to reengineer surviving salivary gland tissue, cell-based transplant therapy, use of bioengineered glands, and development of drugs/biologics to stimulate in vivo regeneration or increase secretion. Understanding the genetic and cellular mechanisms required for development and homeostasis of adult glands is essential to the success of these proposed treatments. Recent advances in genetic lineage tracing provide insight into epithelial lineage relationships during murine salivary gland development. During early fetal gland development, epithelial cells expressing keratin 14 (K14) Sox2, Sox9, Sox10, and Trp63 give rise to all adult epithelium, but as development proceeds, lineage restriction occurs, resulting in separate lineages of myoepithelial, ductal, and acinar cells in postnatal glands. Several niche signals have been identified that regulate epithelial development and lineage restriction. Fibroblast growth factor signaling is essential for gland development, and other important factors that influence epithelial patterning and maturation include the Wnt, Hedgehog, retinoic acid, and Hippo signaling pathways. In addition, other cell types in the local microenvironment, such as endothelial and neuronal cells, can influence epithelial development. Emerging evidence also suggests that specific epithelial cells will respond to different types of salivary gland damage, depending on the cause and severity of damage and the resulting damaged microenvironment. Understanding how regeneration occurs and which cell types are affected, as well as which signaling factors drive cell lineage decisions, provides specific targets to manipulate cell fate and improve regeneration. Taken together, these recent advances in understanding cell lineages and the signaling factors that drive cell fate changes provide a guide to develop novel regenerative treatments.

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STEM Cells and Liver Carcinogenesis: Contributions of Light, Confocal and Electron Microscopy

Microscopy and Microanalysis ◽

10.1017/s1431927600006905 ◽

1997 ◽

Vol 3 (S2) ◽

pp. 3-4

Author(s):

P. M. Novikoff ◽

A. Yam

Keyword(s):

Electron Microscopy ◽

Partial Hepatectomy ◽

Cell Lineage ◽

Cell Types ◽

Liver Carcinogenesis ◽

Hepatic Parenchyma ◽

Hepatocyte Regeneration ◽

Bile Ductule ◽

Parenchymal Hepatocytes ◽

Confocal And Electron Microscopy

Three cell types not previously described were revealed by the application of several microscopic procedures in combination with cytochemistry and irnmunocytochemistry in the livers of rats treated according to the Solt et al carcinogenesis protocol. This protocol consists of the administration of an initiating carcinogen (diethynitrosamine), a mitoinhibitory carcinogen, (acethylaminofluorene) and a growth stimulus (partial hepatectomy) (1). Two of the cell types were found in intrahepatic bile ductules and one within the connective tissue stroma surrounding the ductules. These findings have implications for understanding the cell lineage pathways that operate in an experimental rodent hepatocarcinogenesis system in which hepatocyte regeneration is inhibited and in which preneoplastic nodules and hepatomas develop. Our previous studies have determined some of the enzymatic, antigenic and structural properties of these cell types and their interrelations to each other, to parenchymal hepatocytes and to preneoplastic nodules (2).Proliferation of bile ductule cells occurs early (24-48 hrs) after the partial hepatectomy step of the protocol with extensive branching of the ductules into the hepatic parenchyma.

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