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Results for “Transdifferentiation”

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At least 919 records · Page 51Linked to original sources
PubMed1986

Induction of hepatocytes in the pancreas of copper-depleted rats following copper repletion.

Pancreatic hepatocytes are induced in rats maintained on copper-deficient diet containing 0.6% D-penicillamine for 8-10 weeks, followed by copper repletion. These induced hepatocytes are morphologically and functionally very similar to parenchymal cells of the liver. Immunofluorescence stains demonstrated the presence of albumin and catalase in these cells. Stains for pancreatic enzymes and hormones were negative. As expected, the hypolipidemic compound, ciprofibrate, induced peroxisome proliferation in these cells. These results indicate that a simple depletion and repletion of copper can trigger transdifferentiation in the pancreas of adult rats.

Albumins↗
PubMed1994

Patterns of cell movement within the Dictyostelium slug revealed by cell type-specific, surface labeling of living cells.

There are cells scattered in the rear, prespore region of the Dictyostelium slug that share many of the properties of the prestalk cells and that are therefore called anterior-like cells (ALCs). By placing the gene encoding a cell surface protein under the control of an ALC-specific promoter and immunologically labeling the living cells, we analyze the movement of ALCs within the slug. There is a posterior to anterior cellular flow, and the ALCs change their movement pattern as they enter the prestalk zone. Prestalk cells are periodically shed from the migrating slug. They must be replaced if the correct ratio of prestalk to prespore cells is to be maintained, and we present evidence for the transdifferentiation of prespore into prestalk cells, with ALCs functioning as intermediates in the transition. The slug has, therefore, a surprisingly dynamic structure, both with respect to cellular differentiation and cell movement.

Amino Acid Sequence↗
PubMed1981

Ultrastructure of growth cones formed by isolated rat adrenal medullary chromaffin cells in vitro after treatment with nerve growth factor.

Growth cones formed by adrenal chromaffin cells from young postnatal rats cultured in the presence of nerve growth factor (NGF) were studied at an electron microscopic level. These growth cones are similar in many respects to those formed by sympathetic neurons in vitro supporting the view that NGF-treated chromaffin cells may undergo neuronal transdifferentiation.

Adrenal Medulla↗
PubMed1992

Retinal regeneration.

The goal of research on neural regeneration is to restore brain function following injury. To many, this suggests regrowing damaged axons and re-establishing the interrupted pathways. A second, but little studied aspect of brain regeneration, is the replacement of lost neurons. For example, in some animals the neural retina is reconstituted by regenerative neurogenesis following its partial or total destruction. Two separate processes underlying retinal regeneration have been described: transdifferentiation of retinal pigmented epithelial cells into retinal neural progenitors (in adult urodeles, tadpoles, and embryonic chickens), and alteration in the fate of photoreceptor progenitors intrinsic to the retina (in adult fish).

Animals↗
PubMed1989

Cellular 'neoteny': a possible developmental basis for chromaffin cell plasticity.

Adrenal medullary chromaffin cells, SIF cells and sympathetic neurons are derived from the sympatho-adrenal sublineage of the neural crest, and represent a range of cellular phenotypes extending from endocrine to neuronal. It is suggested here that these cell types may represent different stages of developmental 'arrest' along a linear pathway whose endpoint is a cholinergic sympathetic neuron. This model explains the 'transdifferentiation' of mature cells seen in this system as simply a delayed realization of transitions that normally occur between these stages during development. Such a 'linear model' of phenotypic diversification may be applicable to other developing systems that generate closely related but distinct cell types.

Adrenal Medulla↗
PubMed1995

Transformations between epithelium and mesenchyme: normal, pathological, and experimentally induced.

In this review, we define the two major tissue types, epithelium and mesenchyme, and we describe the transformations (transdifferentiations) of epithelium to mesenchyme (EMT) and mesenchyme to epithelium (MET) that occur during embryonic development. The differentiation of the metanephric blastema provides a striking example of MET. Differentiation of metanephric epithelium is promoted by matrix molecules and receptors (nidogen, laminins, alpha 6 integrins), hepatic growth factor/scatter factor, and products of the genes wnt-1, wnt-4, and Pax-2. Transformation of MDCK epithelium to mesenchyme-like cells is promoted in vitro by antibodies to E-cadherin, products of v-src, v-ras, and v-mos, and by manipulation of the epithelium on collagen gels. Suspension in collagen gel, transforming growth factors, and c-fos have also been shown to promote EMT in epithelia. We present studies from our laboratory showing that alpha 5 beta 1 integrin has a role in the EMT of lens epithelium that is brought about by suspension in collagen gel. Our laboratory has also shown that transfection with the E-cadherin gene induces embryonic corneal fibroblasts to undergo MET and that this MET is enhanced by interaction of the differentiating epithelium with living fibroblasts. This review calls attention to the roles that EMT and MET might have in kidney pathologies and urges further study of the involvement of these phenomena in renal development, renal injury, and renal malignancy.

Animals↗
PubMed1983

Tetanus toxin binding to different morphological phenotypes of cultured rat and bovine adrenal medullary cells.

Tetanus toxin (TT) binding to cultured rat and bovine adrenal medullary cells has been investigated using indirect immunofluorescence and anti-dopamine-beta-hydroxylase (DBH) antibodies as a probe to identify catecholaminergic cells. TT binds to all rat adrenal medullary cells which display a neuronal phenotype induced by treatment with nerve growth factor and/or medium conditioned by C6 glioma cells. In contrast, 90-95% of the rounded DBH-positive cells are TT-negative, suggesting that in vitro-transdifferentiation of rat chromaffin cells alternates the expression of membrane properties. Cultured bovine chromaffin cells have no TT binding sites independent of their morphological phenotype.

Adrenal Medulla↗
PubMed1996

New hair cells arise from supporting cell conversion in the acoustically damaged chick inner ear.

Supporting cell mitosis contributes significantly to hair cell regeneration in the acoustically damaged bird inner ear. Yet there may be another mechanism of hair cell replacement: supporting cell conversion. This study used cytosine arabinoside (Ara-C), an inhibitor of DNA synthesis, to better determine whether supporting cells could transdifferentiate into hair cells without cell division. Chicks received Ara-C injections after acoustic overstimulation. Scanning microscopic studies of the basilar papillae revealed several unpaired, immature hair cells. To ensure Ara-C's blockage of DNA synthesis, one group of birds received both Ara-C and bromodeoxyuridine (BrdU), while another group had BrdU only. Immunocytochemical analysis of Ara-C/BrdU and BrdU papillae indicated zero and 16 dividing cells, respectively. This difference confirmed that Ara-C blocked DNA synthesis, arresting supporting cell mitosis. These data strongly suggest that supporting cell can convert into hair cells.

Animals↗
PubMed1994

CNTF, FGF, and NGF collaborate to drive the terminal differentiation of MAH cells into postmitotic neurons.

The differentiation of neuronal cell progenitors depends on complex interactions between intrinsic cellular programs and environmental cues. Such interactions have recently been explored using an immortalized sympathoadrenal progenitor cell line, MAH. These studies have revealed that depolarizing conditions, in combination with exposure to FGF, can induce responsiveness to NGF. Here we report that CNTF, which utilizes an intracellular signaling pathway distinct from that of both FGF and NGF, can collaborate with FGF to promote efficiently the differentiation of MAH progenitor cells to a stage remarkably reminiscent of NGF-dependent, postmitotic sympathetic neurons. We also find that similar collaborative interactions can occur during transdifferentiation of normal cultured chromaffin cells into sympathetic neurons.

Animals↗
PubMed1994

Gene regulation and differentiation in vertebrate ocular tissues.

Molecular biological techniques have contributed greatly to the study of vertebrate ocular tissues. The specification of ocular tissues has been shown to be closely related to the expression of transcription factors encoded by genes such as Pax6 and microphthalmia. Lens-specific expression of the delta 1-crystallin gene is controlled by factors, such as delta EF1, binding to its enhancer sequences. Retinal activity of the glucocorticoid hormone receptor is regulated by its binding with another transcription factor. Degeneration of photoreceptors in a retinal disease, retinitis pigmentosa, can be caused by the introduction of a mutated opsin gene into mice. In addition, the process of transdifferentiation in ocular tissues has been described at the level of gene expression.

Animals↗
PubMed2006

Palatal fusion - where do the midline cells go? A review on cleft palate, a major human birth defect.

Formation of the palate, the organ that separates the oral cavity from the nasal cavity, is a developmental process characteristic to embryos of higher vertebrates. Failure in this process results in palatal cleft. During the final steps of palatogenesis, two palatal shelves outgrowing from the sides of the embryonic oronasal cavity elevate above the tongue, meet in the midline, and rapidly fuse together. Over the decades, multiple mechanisms have been proposed to explain how the superficial mucous membranes disappear from the contact line, thus allowing for normal midline mesenchymal confluence. A substantial body of experimental evidence exists for cell death, cell migration, epithelial-to-mesenchymal transdifferentiation (EMT), replacement through new tissue intercalation, and other mechanisms. However, the most recent use of gene recombination techniques in cell fate tracking disfavors the EMT concept, and suggests that apoptosis is the major fate of the midline cells during physiological palatal fusion. This article summarizes the benefits and drawbacks of histochemical and molecular tools used to determine the fates of cells within the palatal midline. Mechanisms of normal disintegration of the midline epithelial seam are reviewed together with pathologic processes that prevent this disintegration, thus causing cleft palate.

Animals↗
PubMedDate not supplied

Regeneration of beta-cells and neogenesis from small ducts or acinar cells promote recovery of endocrine pancreatic function in alloxan-treated rats.

BACKGROUND: We previously showed by using biochemical parameters that male Sprague-Dawley rats receiving a single intraperitoneal (i.p.) administration of alloxan (120 mg/kg body weight) with no further treatment recovered endocrine pancreatic function after 12 days. METHODS: Male Sprague-Dawley rats received an i.p. injection of alloxan (120 mg/kg body wt), were killed at 3, 6, 9, or 12 days (n=7), and their capacity to recover endocrine function was evaluated by means of a) biochemical parameters, which included glucose, triglyceride, and total cholesterol measurements and b) nuclear incorporation of 5'-bromodeoxyuridine (BrdU) by beta and acinar cells as well as presence of neogenesis from either ductal or acinar cells using double-staining BrdU-insulin immunohistochemical technique. RESULTS: Three days after receiving a single i.p. administration of alloxan, rats showed increase in serum glucose, triglyceride, and total cholesterol concentrations, reaching levels of 542.4+/-63.1, 907.6+/-154.9, and 106.0+/-2.7 mg/dL (mean+/-standard deviation [SD]), respectively. At this time, increase in beta-cell replication was also observed, although this reached maximum by day 6 (p <0.001). Replication was also present in acinar cells, but these cells showed their maximum at day 3 (p <0.001) and subsequently decreased, as did beta-cells, almost steadily to normal values by day 12. Neogenesis of beta-cells was observed mainly as transdifferentiation from acinar cells at day 3 and from ductal cells at day 6, after which it tended to be normal. CONCLUSIONS: Male Sprague-Dawley rats receiving a single i.p. alloxan dose tended to normalize their endocrine function by day 12 after alloxan administration. This process included both regeneration and neogenesis of pancreatic beta-cells from either ductal or acinar cells.

Alloxan↗
PubMed2026

Athero-oncology: Vascular smooth muscle cell tumor-like transformation in atherosclerosis and therapeutic opportunities.

Atherosclerosis (AS) is the main pathological basis of cardiovascular diseases, and its pathogenesis and treatment strategies remain major challenges. Recent advances in single-cell RNA sequencing and lineage tracing have revealed that vascular smooth muscle cells (VSMCs) are not merely passive structural components of atherosclerotic plaques, but highly plastic participants that undergo clonal expansion, phenotypic modulation, and transdifferentiation into functionally diverse cell states. These findings have prompted the emergence of an "athero-oncology" framework, which explores selected tumor-like cellular programs in VSMCs during AS without equating atherosclerosis with cancer. In this review, we summarize the evidence supporting VSMC-derived clonal expansion and phenotypic diversification in atherosclerotic lesions and discuss key mechanisms involved in this process, including proliferative expansion and survival programs, metabolic reprogramming, epigenetic regulation, DNA damage and genomic stress, VSMC senescence, pathological angiogenesis, and remodeling of the inflammatory and immune microenvironment. We further highlight shared signaling pathways between VSMC-driven plaque remodeling and tumor biology, while emphasizing fundamental differences between AS and malignant disease in growth limitation, mutational burden, metastatic potential, and clinical behavior. Finally, we discuss oncology-inspired therapeutic opportunities and boundaries, including pathway-level targeting of proliferative, metabolic, epigenetic, and inflammatory programs, as well as the risks of directly repurposing anticancer therapies for chronic vascular disease. This framework may provide new insights into vascular biology and therapeutic development.

atherosclerosis↗
PubMed2005

Autoantibody-associated congenital heart block: TGFbeta and the road to scar.

Few diseases exemplify the integration of research from bench to bedside as well as neonatal lupus (NL), often referred to as a model of passively acquired autoimmunity. The signature histologic lesion of autoimmune congenital heart block (CHB) is fibrosis of the conducting tissue and, in some cases, the surrounding myocardium. It is astounding how rapid, and in most cases, irreversible, the fibrotic response to injury is. The mechanism by which maternal anti-SSA/Ro-SSB/La antibodies initiate and finally eventuate in atrioventricular (AV) nodal scarring is not yet defined. In vitro and in vivo studies suggest that one pathologic cascade leading to scarring may be initiated via apoptosis, resulting in the translocation of SSA/Ro-SSB/La antigens and surface binding by maternal autoantibodies. Subsequently, the Fc portion of the bound immunoglobulin engages Fcgamma receptors on tissue macrophages, resulting in the release of TGFbeta at a threshold that favors a pro-fibrotic milieu and irreversible scarring. This cascade also involves a tissue-specific activation of TGFbeta, which promotes the transdifferentiation of fibroblasts into myofibroblasts, a scarring phenotype. Phagocytosis of opsonized apoptotic cardiocytes is distinct from macrophage pathways engaged in physiologic clearance of dying tissue, which also results in the release of TGFbeta but in the latter case appropriately serves to dampen inflammation. Downregulation of TGFbeta (activation/secretion pathway) may provide the basis of a novel approach to treatment of CHB in the future.

Atrioventricular Node↗
PubMed2005

Statins and the vasculopathy of systemic sclerosis: potential therapeutic agents?

It has been postulated that endothelial cell injury is the initiating event in the pathogenesis of systemic sclerosis, causing attraction, attachment, migration and infiltration of activated T-cells and subsequent production of cytokines and growth factors. As a result of the action of these cytokines and growth factors, chemoattraction of fibroblasts into the vessel wall and transdifferentiation of resident fibroblasts and smooth muscle cells into myofibroblasts occur leading to fibrosis and exaggerated collagen deposition in the vessel wall. To date, the therapeutic options for the vasculopathy of systemic sclerosis have been limited to drugs that cause vasodilation and inhibit platelet aggregation and only a few agents have shown vascular remodeling effects. Therapeutic agents that could potentially modify the course of this vasculopathy may have a disease-modifying effect, particularly, if instituted in the early stages of the disease. Extensive recent studies have shown that statins display numerous effects independent of their well-established lipid-lowering effect that may be of potential benefit in preventing vascular injury and ischemic vascular events. Here, we review the current literature, which suggests that statins may have a modifying effect on the vasculopathy of systemic sclerosis.

Animals↗
PubMed2005

Liver stem cell-derived beta-cell surrogates for treatment of type 1 diabetes.

Consistent with the common embryonic origin of liver and pancreas as well the similar glucose-sensing systems in hepatocytes and pancreatic beta-cells, it should not be surprising that liver stem cells/hepatocytes can transdifferentiate into insulin-producing cells under high-glucose culture conditions or by genetic reprogramming. Persistent expression of the pancreatic duodenal homeobox-1 (Pdx1) transcription factor or its super-active form Pdx1-VP16 fusion protein in hepatic cells reprograms these cells into pancreatic beta-cell precursors. In vitro culture at elevated glucose concentrations or in vivo exposure to a hyperglycemia are required for further differentiation and maturation of liver-derived pancreatic beta-cell precursor into functional insulin-producing pancreatic beta-like cells. Under appropriate conditions, multiple pancreatic transcription factors can work in concert to reprogram liver stem/adult liver cells into functional insulin-producing cells. If such autologous liver-derived insulin-producing cells can be made to escape the type 1 diabetes-associated autoimmunity, they may serve as a valuable cell source for future cell replacement therapy without the need for life-long immunosuppression.

Animals↗
PubMed2003

Ectopically expressed PDX-1 in liver initiates endocrine and exocrine pancreas differentiation but causes dysmorphogenesis.

To date, the potency of pancreatic and duodenal homeobox gene 1 (PDX-1) in inducing differentiation into insulin-producing cells has been demonstrated in some cells and tissues. In order to carry out efficient screening of somatic tissues and cells that can transdifferentiate into beta-cell-like cells in response to PDX-1, we generated CAG-CAT-PDX1 transgenic mice carrying a transgene cassette composed of the chicken beta-actin gene (CAG) promoter and a floxed stuffer DNA sequence (CAT) linked to PDX-1 cDNA. When the mice were crossed with Alb-Cre mice, which express the Cre recombinase driven by the rat albumin gene promoter, PDX-1 was expressed in more than 50% of hepatocytes and cholangiocytes. The PDX-1 (+) livers expressed a variety of endocrine hormone genes such as insulin, glucagon, somatostatin, and pancreatic polypeptide. In addition, they expressed exocrine genes such as elastase-1 and chymotrypsinogen 1B. However, the mice exhibited marked jaundice due to conjugated hyperbilirubinemia, and the liver tissue displayed abnormal lobe structures and multiple cystic lesions. Thus, the in vivo ectopic expression of PDX-1 in albumin-producing cells was able to initiate but not complete the differentiation of liver cells into pancreatic cells. The conditional PDX-1 transgenic mouse system developed in this study appeared to be useful for efficient screening of PDX-1 responsive somatic tissues and cells.

Animals↗
PubMed2004

N(6)-Methyldeoxyadenosine, a nucleoside commonly found in prokaryotes, induces C2C12 myogenic differentiation.

N(6)-methyl-2(')-deoxyadenosine (MedAdo) is a nucleoside naturally found in prokaryotic DNA. Interestingly, the N(6)-methylation of adenine in DNA seems to have been counter-selected during the course of evolution since MedAdo has not been detected in mammalian DNA until now. We show here that treatment with MedAdo induces myogenesis in C2C12 myoblasts. The presence of MedAdo in C2C12 DNA was investigated using a method based on HPLC coupled to electrospray ionization tandem mass spectrometry which is several thousand fold more sensitive than assays used previously. By this procedure, MedAdo is detected in the DNA from MedAdo-treated cells but remains undetectable in the DNA from control cells. Furthermore, MedAdo regulates the expression of p21, myogenin, mTOR, and MHC. Interestingly, in the pluripotent C2C12 cell line, MedAdo drives the differentiation towards myogenesis only. Thus, the biological effect of MedAdo is suppressed in the presence of BMP-2 which transdifferentiates C2C12 from myogenic into osteogenic lineage cells. Taken together these results point to MedAdo as a novel inducer of myogenesis and further extends the differentiation potentialities of this methylated nucleoside. Furthermore, these data raise the intriguing possibility that the biological effects of MedAdo on cell differentiation may have led to its counter-selection in eukaryotes.

Adenine↗