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Showing papers on "Transdifferentiation published in 1998"


Journal ArticleDOI
TL;DR: P phenotypic and morphological evidence is provided to support the hypothesis that TEC are pro-fibrogenitor cells capable of tubular epithelial-myofibroblast transdifferentiation in progressive renal fibrosis.

396 citations


Journal ArticleDOI
TL;DR: Data suggest an involvement of the TGF-alpha/EGFR pathway in conjunction with other yet unknown events in pancreatic tumor development and observations are in favor of an acinar-ductal carcinoma sequence.

198 citations


Journal ArticleDOI
TL;DR: It is concluded that there is as yet no evidence for the existence of “dormant” stem cells in the adult pancreas, and there is some evidence, however, that differentiated exocrine acinar and/or duct cells retain the capacity to transdifferentiate into insulin‐expressing beta‐cells.
Abstract: The pancreas is composed of at least three types of differentiated tissue: the hormone-containing cells in islets (4 different cell types), the exocrine zymogen-containing acini, and the centroacinar cells, ductules and ducts (ductal tree). All of these cells appear to have a common origin during embryogenesis in the form of duct-like protodifferentiated cells. Later in life, the acinar and ductal cells retain a significant proliferative capacity that can ensure cell renewal and growth, whereas the islet cells become mitotically inactive. Interestingly, new islet cells, including the insulin-producing beta-cells, can regenerate after tissue injury by a process called neogenesis. The neogenetic process involves differentiation of duct-like (exocrine) epithelial cells to hormone-expressing cells. In this paper, we review the question whether islet beta-cell regeneration or neogenesis in the pancreas depends on "embryonic-like" stem cells or on transdifferentiation of "fully differentiated" cells. This issue is important to find the right model for in vitro research aiming at controlling the process of beta-cell neogenesis. The latter could lead to applications in the treatment of diabetes where functional beta-cells are deficient. We conclude from the available evidence that there is as yet no evidence for the existence of "dormant" stem cells in the adult pancreas. There is some evidence, however, that differentiated exocrine acinar and/or duct cells retain the capacity to transdifferentiate into insulin-expressing beta-cells.

183 citations


Journal ArticleDOI
TL;DR: An unexpected plasticity of the adult vascular smooth muscle cell phenotype is suggested and cartilaginous metaplasia of the arterial wall is provided and TGF-beta1 withdrawal is associated with regression of vascular lesions.
Abstract: Uninjured rat arteries transduced with an adenoviral vector expressing an active form of transforming growth factor β1 (TGF-β1) developed a cellular and matrix-rich neointima, with cartilaginous metaplasia of the vascular media. Explant cultures of transduced arteries showed that secretion of active TGF-β1 ceased by 4 weeks, the time of maximal intimal thickening. Between 4 and 8 weeks, the cartilaginous metaplasia resolved and the intimal lesions regressed almost completely, in large part because of massive apoptosis. Thus, locally expressed TGF-β1 promotes intimal growth and appears to cause transdifferentiation of vascular smooth muscle cells into chondrocytes. Moreover, TGF-β1 withdrawal is associated with regression of vascular lesions. These data suggest an unexpected plasticity of the adult vascular smooth muscle cell phenotype and provide an etiology for cartilaginous metaplasia of the arterial wall. Our observations may help to reconcile divergent views of the role of TGF-β1 in vascular disease.

181 citations


Journal ArticleDOI
TL;DR: The observation that activated stellate cells in culture can express leptin has implications for understanding adipocyte biology in liver disease and treatment of malnutrition in cirrhotics.

174 citations


Journal ArticleDOI
TL;DR: Results showed that downregulation of Mitf expression is essential for the transdifferentiation of rPEC differentiation, and suggested that pax6 regulates pax 6 expression negatively.

137 citations


Journal ArticleDOI
TL;DR: It is demonstrated that both soluble factors and alterations in cell shape modulate T1α expression in parallel with AEC phenotype and provide further support for the concept that transdifferentiation between AT2 and AT1 cell phenotypes is at least partially reversible.
Abstract: T1α is a recently identified gene expressed in the adult rat lung by alveolar type I (AT1) epithelial cells but not by alveolar type II (AT2) epithelial cells. We evaluated the effects of modulatin...

98 citations


Journal ArticleDOI
TL;DR: Results strongly suggest that the silver phenotype is caused by the mutation of Mitf and that Mitf plays a critical role in rPEC differentiation and transdifferentiation.

85 citations


Journal ArticleDOI
TL;DR: Increasing evidence suggests that regeneration/repair of mammalian auditory hair cells is possible during the early neonatal period and may exist to a very limited degree at later times.

66 citations


Journal ArticleDOI
TL;DR: Differentiation of the regenerating structures to replace cells such as S1–containing neurons, is thought to involve cell cycle activity and differentiation of epithelial cells in the epidermal tissue, possibly in association with certain types of coelomocytes which move into the Regenerating area.
Abstract: Regeneration of the arm of the starfish, Asterias rubens (L.) (Echinodermata: Asteroidea) was examined using two preparations. The first involved regeneration of the entire arm tip and its associated sensory structures and the second examined regeneration of a small section of radial nerve cord in the mid–arm region. Cell cycle activity was investigated by incorporation of the thymidine analogue, bromodeoxyuridine (BrdU). Details of neuroanatomy were obtained by immunocytochemistry (ICC) using an antiserum to the recently isolated starfish neuropeptide, GFNSALMFamide (S1). BrdU labelling indicated that initial events occur by morphallaxis, with cell cycle activity first apparent after formation of a wound epidermis. As regeneration proceeded, BrdU immunoreactive (IR) nuclei revealed cell cycle activity in cells at the distal ends of the radial nerve cord epidermis, in the coelomic epithelium, the perihaemal and water vascular canal epithelia, and in the forming tube feet of both preparations. By varying the time between BrdU pulses and tissue fixation, the possible migration or differentiation of labelled cells was investigated. Neuropeptide ICC indicated the extension of S1–IR nerve fibres into the regenerating area, soon after initial wound healing processes were complete. These fibres were varicose and disorganized in appearance, when compared to the normal pattern of S1–IR in the radial nerve. S1–IR was also observed in cell bodies, which reappeared in the reforming optic cushion and radial nerve at later stages of regeneration. Double labelling studies with anti–BrdU and anti–S1 showed no co–localization in these cell bodies, in all the stages examined. It appeared that S1–IR cells were not undergoing, and had not recently undergone, cell cycle activity. It cannot be confirmed whether S1–IR neurons were derived from proliferating cells of epithelial origin, or from transdifferentiation of epithelial cells, although the former mechanism is suggested. Differentiation of the regenerating structures to replace cells such as S1–containing neurons, is thought to involve cell cycle activity and differentiation of epithelial cells in the epidermal tissue, possibly in association with certain types of coelomocytes which move into the regenerating area.

65 citations


Journal ArticleDOI
TL;DR: The results show that apoptosis is responsible for hair cell losses and that cell proliferation occurs in the region of the outer spiral sulcus but not in the area of Deiters cells and pre-existing hair cells, and suggest that celliferation maintains a certain homeostasis in the number of non-sensory cells and participates in epithelial scar formation.
Abstract: Recently, an attempt at cochlear hair cell neodifferentiation has been reported in amikacin-treated rats. In the present study, we aimed to ascertain whether hair cell losses are mediated by apoptosis and whether cell proliferation occurs in damaged intoxicated cochleas. The results show that apoptosis is responsible for hair cell losses and that cell proliferation occurs in the region of the outer spiral sulcus but not in the region of Deiters cells and pre-existing hair cells. We suggest that cell proliferation maintains a certain homeostasis in the number of non-sensory cells and participates in epithelial scar formation. Neodifferentiated cells therefore probably arise from direct transdifferentiation, which could be triggered by phagocytosis of apoptotic bodies.

Journal ArticleDOI
TL;DR: Northern blot data indicates that the up-regulation of pax-6 gene could be an important event during lens regeneration as well as during normal lens development and provides a useful opportunity for analyzing cellular and molecular mechanism involved in each step of transdifferentiation.

Journal Article
TL;DR: Although p53 remains cytoplasmically sequestered in a punctate pattern in N- type cells after DNA damage, the protein is diffusely distributed in the S-type cells and is additionally capable of translocating to the nucleus and mediating a biological response to this damage.
Abstract: Neuroblastoma (NB) cells in vitro are capable of bidirectional transdifferentiation, resulting in two distinct, yet reversible, phenotypes of neuroblastic (N-type) and nonneuronal (S-type) Schwann-like cells. Our previous studies suggested that the wild-type p53 protein is subject to differential regulation in a subset of neuronal cell types. To further test this hypothesis, we compared p53 function in three matched pairs of N- and S-type cell lines, each pair originating from an individual NB tumor. Our data show that although p53 remains cytoplasmically sequestered in a punctate pattern in N-type cells after DNA damage, the protein is diffusely distributed in the S-type cells and is additionally capable of translocating to the nucleus and mediating a biological response to this damage. Our data, therefore, suggest that the p53 protein may be differentially regulated by a neuronal cellular environment and that the sequestration of p53 in NB may be reversible.

Journal ArticleDOI
TL;DR: Results suggest that both smooth muscle and migratory myoblasts contribute to the development of myotubes in the avian iris and that this process is regulated in a non-cell-autonomous fashion by locally generated signals.

Journal ArticleDOI
TL;DR: Deciphering the molecular cues that determine cell plasticity is prerequisite for establishing a unifying concept of mammary gland development and breast tumor progression.
Abstract: The functional unit of the mammary gland is the epithelium. It consists of luminal epithelial cells and myoepithelial cells that are generated from self-renewing stem and progenitor cells. The latter two cell types are scattered throughout the mammary epithelium and are concentrated in specialized structures, the end buds. In transplantation studies the pluripotency of mammary stem cells has been confirmed by demonstrating that they can regenerate a complete mammary gland. The ability of mammary epithelial cells to produce an elaborate ductal system during puberty and to differentiate into milk-producing alveoli during pregnancy is not only influenced by their genetic make-up, but is also governed by local molecular signals. Recent studies suggest that the transdifferentiation of epithelial cells into tumor cells is under microenvironmental control, despite the prominence of genetic mutations in breast cancer. Consequently, disturbances of tissue homeostasis can alter mammary gland development or result in preneoplastic and neoplastic pathologies. The plasticity of mammary epithelia is not limited to the entry of cells into differentiation and transdifferentiation pathways, but extends to their ability to regain facets of their preceding stage of functionality. Deciphering the molecular cues that determine cell plasticity is prerequisite for establishing a unifying concept of mammary gland development and breast tumor progression.

Journal ArticleDOI
TL;DR: It is concluded that lens colony formation in vitro does occur by direct transdifferentiation and not by clonal proliferation of progenitor cells.
Abstract: Transdifferentiation is the process by which differentiated cells alter their identity to become other, distinct cell types. The conversion of neural retina into lens epithelium is one of the most spectacular examples of transdifferentiation. We show that the redirection of cell fate from neural retina to lens and subsequent transdifferentiation is independent of cell replication as it occurs in growth-arrested cell populations. Using DNA ratiometry of individual cells in these cultures we show that, indeed, individual amitotic cells do transdifferentiate. Hence, choice of fate in transdifferentiating cells does not rely on a "community effect" but instead can be categorized as a For lack of overt lens progenitors, and most importantly, for its mitotic independence, we conclude that lens colony formation in vitro does occur by direct transdifferentiation and not by clonal proliferation of progenitor cells.

Journal ArticleDOI
TL;DR: The trans Differentiation of RPE cells to the lentoid structure in this study was in contrast to their transdifferentiation to the retina, as reported in a previous study.
Abstract: To test transdifferentiation of retinal pigment epithelial (RPE) cells in suspension culture, chick embryonic RPE sheets and dissociated RPE cells were cultured for two months in a non-adherent dish for suspension culture. RPE cells, isolated as a sheet, aggregated immediately and remained the same size with their differentiated characteristics for two months. The presence of basic fibroblast growth factor (bFGF) at concentrations of 10 ng/ml or higher induced the formation of a spherical lentoid structure which was positive for crystallin and bFGF receptor. In contrast, dissociated RPE cells did reaggregate but did not develop the lentoid structure even in the presence of bFGF. The transdifferentiation of RPE cells to the lentoid structure in this study was in contrast to their transdifferentiation to the retina, as reported in a previous study.


Journal ArticleDOI
TL;DR: Experiments in which either transcription or translation have been inhibited by actinomycin D and cycloheximide have now shown that the corneal cells are unable to transdiffer‐entiate into lens fibres, indicating that the multi‐step process lens‐transdifferentiation of cornea cells can be controlled also at these levels.
Abstract: The isolated outer cornea cultured in presence of acidic Fibrob‐last Growth Factor (aFGF) can reprogramme its differentiation into lens fibres. The capacity of aFGF to promote lens differentiation is not linked to its mitogenic activity. In previous studies (Bosco et al., 1997) it was observed that the lens transdifferentiation of corneal cells occurs also when DNA replication and cell proliferation are prevented by addition of aphidicolin (a specific inhibitor of DNA polymerase in eukaryotes), to the culture medium. Experiments in which either transcription or translation have been inhibited by actinomycin D and cycloheximide, respectively, have now shown that the corneal cells are unable to transdiffer‐entiate into lens fibres. These results indicate that the multi‐step process lens‐transdifferentiation of corneal cells can be controlled also at these levels.

Book ChapterDOI
01 Jan 1998
TL;DR: Tractional Retinal detachment is a common final pathway to a number of different pathological entities, including trauma, rhegmatogenous retinal detachment and diabetic retinopathyl, and the various stages can be characterized as wound healing or response mechanisms.
Abstract: Tractional retinal detachment is a common final pathway to a number of different pathological entities, including trauma, rhegmatogenous retinal detachment and diabetic retinopathyl. Fundamentally, the various stages of this peculiar process can be characterized as wound healing or response mechanisms. Triggered by an inciting event which disturbs the physioanatomy of the posterior segment, the subsequent breakdown of the vitreo-and blood—retinal barrier leads to the dispersion, migration and proliferation of ocular and non-ocular cells in the vitreous cavity2. The development of a contractile scar-like tissue ultimately results in deleterious vitreoretinal traction3.