Sub-Areas to Transdifferentiation:
Bone Marrow Cells
(2)
Cell Fusion
(2)
(Journal Article): Rearrangements of desmosomal and cytoskeletal proteins during the transition from epithelial to fibroblastoid organization in cultured rat bladder carcinoma cells.
Boyer B, Tucker GC, Valles AM, Franke WW, Thiery JP (Laboratoire de Physiopathologie du Developpement, Centre National de la Recherche Scientifique, Paris, France.)
IN:
J Cell Biol
1989; 109(4 Pt 1):1495-1509
Impact Factor(s) of J Cell Biol: 11.602 (2004), 12.023 (2003), 12.915 (2001)
ABSTRACT: Changes of cell morphology and the state of differentiation are known to play important roles in embryogenesis as well as in carcinogenesis. Examples of particularly profound changes are the conversions of epithelial to mesenchymal cells; i.e., the dissociation of some or all polygonal, polar epithelial cells and their transformation into elongate, fibroblastoid cells of high motility. As an in vitro model system for such changes in cell morphology, we have used cell cultures of the rat bladder carcinoma-derived cell line NBT-II which, on exposure to inducing medium containing a commercial serum substitute (Ultroser G), show an extensive change in their organization (epithelial-mesenchymal transition): the junctions between the epithelial cells are split, the epithelial cell organization is lost, and the resulting individual cells become motile and assume a spindle-like fibroblastoid appearance. Using immunofluorescence microscopy and biochemical protein characterization techniques, we show that this change is accompanied by a redistribution of desmosomal plaque proteins (desmoplakins, desmoglein, plakoglobin) and by a reorganization of the cytokeratin and the actin-fodrin filament systems. Moreover, intermediate-sized filaments of the vimentin type are formed in the fibroblastoid cells. We demonstrate that the modulation of desmosomal proteins, specifically an increase in soluble desmoplakins, is a relatively early event in cell dissociation and in epithelial-mesenchymal transition. In this process, a latent period of 5 h upon addition of inducing medium precedes the removal of these desmosomal components from the plasma membrane. The transition, which is reversible, is dependent on continued protein synthesis and phosphorylation but not on the presence of the inducing medium beyond the initial 2-h period. We discuss the value of this experimental system as a physiologically relevant approach for studying the regulation of the assembly and disassembly of desmosomes and other intercellular adhesion structures, and as a model of the conversion of cells from one state of differentiation into another.
TYPE OF PUBLICATION: Original article
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(Journal Article): Epithelial-to-mesenchymal transition generates proliferative human islet precursor cells.
Gershengorn MC, Hardikar AA, Wei C, Geras-Raaka E, Marcus-Samuels B, Raaka BM (Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-8029, USA.,
marving@intra.niddk.nih.gov
)
IN:
Science
2004; 306(5705):2261-2264
Impact Factor(s) of Science: 30.927 (2005), 31.853 (2004), 29.162 (2003), 26.682 (2002), 23.329 (2001)
ABSTRACT: Insulin-expressing beta cells, found in pancreatic islets, are capable of generating more beta cells even in the adult. We show that fibroblast-like cells derived from adult human islets donated postmortem proliferate readily in vitro. These mesenchymal-type cells, which exhibit no hormone expression, can then be induced to differentiate into hormone-expressing islet-like cell aggregates, which reestablishes the epithelial character typical of islet cells. Immunohistochemistry, in situ hybridization, and messenger RNA measurements in single cells and cell populations establish the transition of epithelial cells within islets to mesenchymal cells in culture and then to insulin-expressing epithelial cells.
TYPE OF PUBLICATION: Original article
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(Journal Article): Morphology and function of cultured human fetal pancreatic cells transplanted into athymic mice: a longitudinal study.
Beattie GM, Butler C, Hayek A (Lucy Thorne Whittier Children's Center, Whittier Institute, CA.)
IN:
Cell Transplant
1994; 3(5):421-425
Impact Factor(s) of Cell Transplant: 2.327 (2003), 2.42 (2002), 2.19 (2001)
ABSTRACT: Islet-like cell clusters generated from human fetal pancreases between 18-24 wk gestation were able to grow and mature both morphologically and functionally after transplantation under the kidney capsule of athymic nude mice. Grafted tissue, predominantly ductal in appearance was unresponsive to glucose 2 wk after grafting. The tissue assumed the trabecular column-like architecture of adult islets by 3 mo, with a concomitant 3-4-fold increase in serum human C-peptide concentration after glucose challenge. Moreover, at that time the surface area of insulin containing cells in the graft increased 20-fold over the starting material. Exocrine components, identified by their characteristic eosinophilic secretory granules were also identified at this time. Transplanted cell clusters were capable of releasing C-peptide for at least 12 mo, when the experiment was terminated. At this time, 1 yr posttransplantation, although the proportion of insulin containing cells in the graft remained unchanged from that measured at 4 mo, a reduction in the magnitude of the C-peptide response to glucose was observed; this finding coincided with a significant mononuclear infiltrate in some areas of the transplanted tissue. In summary, human fetal pancreatic cells grown in tissue culture as cell aggregates, after transplantation under the kidney capsule, remain functionally viable for virtually the life span of immunocompromised rodents. Because of their long-term viability, the use of islet-like cell clusters is a potentially useful method to expand transplantable cells.
TYPE OF PUBLICATION: Original article
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