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Results for “Transdifferentiation”

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At least 271 records · Page 15Linked to original sources
PubMed2004

Proteome profile changes during transdifferentiation of NRP-152 rat prostatic basal epithelial cells.

NRP-152 is an androgen responsive, non-tumorigenic cell line, which shows basal epithelial cell characteristics under normal growth conditions. It has been noted that NRP-152 undergoes morphological and cytoskeletal changes toward its luminal counterpart NRP-154 when it is grown under growth restrictive conditions. We have extensively investigated the details of protein change of NRP-152 during transdifferentiation using proteomic techniques. NRP-152 cells were cultured under normal and growth restrictive media conditions for 3, 5 days. NRP-154 cells were normally cultured. Protein samples were submitted to 2D gel electrophoresis and silver stained. Protein patterns on the gels were comparatively analysed using Melanie III software. Protein spots exhibiting significant changes in NRP-152 cells during the time course were excised and subjected to in-gel tryptic digestion. After 6 days of growth restrictive conditions in NRP-152, the cells were morphologically changed resembling luminal phenotype. Of the 35 protein spots that were up-reglated, 20 proteins from 21 spots were identified by peptide mass fingerprinting and, of 21 proteins spots that were down-regulated, 10 proteins from 12 spots were identified as landmark proteins. Our study confirmed that basal NRP-152 cells were proportionally transdifferentiated into luminal featuring cells according to the duration of growth restrictive culture conditions. This suggests that human prostatic basal epithelial cells may be changed into luminal cells under certain conditions. Proteomic approach enabled us to identify 30 proteins involved in this differentiation with a single experiment. These proteins will be subjected to further functional studies to evaluate their possible roles related to cellular differentiation. These data strongly support that proteomics is a very powerful approach for studying physiologic and pathologic cellular changes such as differentiation and carcinogenesis.

Animals↗
PubMed2004

[Relationship of mitogen-activated protein kinases activation with transdifferentiation of renal tubular epithelial cells in patients with IgA nephropathy].

OBJECTIVE: To investigate the expression patterns of MAPK family (including ERK, JNK and p38) and to analyze the effects of MAPKs on renal tubular epithelial cells (RTEC) transdifferentiation in vivo. METHODS: Renal biopsy specimen were collected from 36 patients with IgA nephropathy (IgAN), which were divided into mild proliferation group (MP), focal proliferation group (FP) and proliferation-sclerosis group (PS) according to the glomerular lesions. Renal tubulointerstitial lesion score was assessed. Positive tubules of PCNA, FN, alpha-SMA, MAPK subtypes expression and phosphorylation in renal tubules were detected by immunohistochemistry staining combined with semi-quantitative method. A correlation analysis was made. RESULTS: In the MP, FP and PS groups of IgAN, the score of tubulointerstitial lesion, the positive stained tubule of PCNA, alpha-SMA and FN expression were more abundant with the severity of glomerular injury. The expression of alpha-SMA in tubule was correlated closely to FN expression and the score of interstitial fibrosis. Distribution of all subtypes of MAPK in renal tissue was no different between IgAN and normal subjects. With the severity of glomerular disease, positive tubules expressed P-ERK or P-JNK increased gradually, especially in PS group, in which expression of P-ERK was 3 fold and P-JNK was 1.6 fold compared to control (P < 0.05). Expression of JNK protein in tubule was enhanced in PS group. Expression of P-p38 had no change in different groups. P-ERK positive tubules correlated to FN expression. CONCLUSION: ERK and JNK are strongly expressed and activated in renal tubules in patients with IgAN. It seems that JNK activation is a critical signal to regulate RTEC transdifferentiation, but ERK activation may play an indirect role on this process.

Actins↗
PubMed2005

[Podocytopathie and transdifferentiation of the podocytes in human glomerulonephritis. An immunomorphological study].

Transdifferentiation is characterized by a loss of normal epitopes by differentiated cells, accompanied by the acquisition of new epitopes and new functions. Podocytes are differentiated epithelial cells that cover and adhere to the outer surface of the glomerular basement membrane (GBM). The podocyte/GBM complex contributes to the selective filter function of the glomerular tuft. We have shown that, in various human glomerulonephritides, "dysregulated" podocytes acquire the potential to proliferate and multiply, undergo profound morphologic changes, detach from the GBM, and show phenotypic changes indicative of transdifferentiation. In the course of these events they lose their original epitopes and acquire macrophagic markers.

Basement Membrane↗
PubMed1990

Conjunctival transdifferentiation is due to the incomplete removal of limbal basal epithelium.

Previous studies have shown that using n-heptanol to create a total corneal epithelial defect beyond the limbus results in two different healing patterns with an unpredictable incidence. Between 14-68% of these wounded rabbit corneas (n = 287, combining various reports) showed extensive vascularization and conjunctivalization, whereas the remaining were not vascularized and had conjunctival transdifferentiation with a cornea-like epithelium. To investigate the role of the limbal epithelium in these two healing patterns, the authors treated rabbit eyes for various durations with n-heptanol and additional scraping. Histology showed that treatment for up to 120 seconds removed both the corneal and conjunctival epithelia but left the limbal basal cells intact. To prove viability, they cultured the treated limbal explants on collagen gel. After 14 days of culture, increased stratification of the limbal epithelium and an epithelial outgrowth onto the corneal stroma was observed. The latter was proven to be of corneal origin (positive to AE-5 but negative to AM-3 monoclonal antibody staining). The authors then surgically removed the entire limbal zone including 2 mm of peripheral cornea and 3 mm of adjacent conjunctiva in addition to n-heptanol debridement of the entire corneal epithelium in 54 rabbit eyes and observed a high incidence (96%) of corneal vascularization and conjunctivalization of the resultant epithelial phenotype (positive to AM-3, but negative to AE-5 monoclonal antibody staining). These results support the hypothesis that corneal epithelial stem cells are located in the limbus and indicate that an incomplete removal of the basal limbal epithelium by n-heptanol leads to unvascularized corneas with conjunctival transdifferentiation. Conversely, complete removal of such cells results in corneal vascularization and conjunctivalization.

Alcohols↗
PubMedDate not supplied

[Fibronectin distribution during the transdifferentiation and proliferation of eye cells after retinal detachment and removal of the crystalline lens in tritons].

Expression of fibronectin (Fn) during eye tissue regeneration in the newt after retinal detachment and lens removal was studied by immunohistochemistry. Proliferation of cells involved in eye tissue regeneration was studied using autoradiography. Fn was detected around the cell membranes of undifferentiated proliferating and migrating cells in ciliary body of the iris and growth zone of the retina. Redistribution of Fn was observed in proliferating cells of the dorsal iris participating in lens regeneration. Fn appeared on the apical surface of proliferating redifferentiating pigment epithelium (PE) cells at the periphery of the eye and over the whole surface of proliferating PE cells in the central part of the eye. The Fn level in the Bruch's membrane decreased in the area of transdifferentiating cells detachment from PE layer (in the lower part of the eye) but continued to be stable in the area of PE cell redifferentiation (at the periphery of the eye). The role of Fn is discussed in relation to transdifferentiation, proliferation and migration of cells in the regenerating eye.

Animals↗
PubMed1988

An ultrastructural study of rabbit ocular surface transdifferentiation.

When debridement of the rabbit cornea is followed by re-epithelialization from the conjunctiva, a process of transdifferentiation of the endothelium occurs. Goblet cells appear peripherally 1 week after healing of the epithelial defect, are widespread at 2 weeks, and disappear centrally at 3 to 4 weeks. Six weeks after closure of the defect, the epithelium has reverted to the customary corneal appearance. The morphology of the regenerating epithelium was studied by light, transmission and scanning electron microscopy. The precursor cells for the goblet cells were identified in stage 1, before PAS-positive cells were present, as pairs of cells with dark cytoplasm and prominent Golgi. Subsequently, goblet cells were present in pairs, indicating that goblet cells are derived from non-goblet epithelial cells, and that they do not simply migrate onto the cornea. At the time of transdifferentiation, loss of goblet cells was shown to occur both by desquamation from the surface and by in situ cell death.

Animals↗
PubMed1982

Transdetermination and transdifferentiation of neural retinal cells into lens in cell culture.

Two aspects of transdifferentiation of avian neural retina (NR) cells into lens in cell culture were discussed. First, by means of the transfer experiments of NR cells pre-cultivated in spreading cultures (SpC) longer than 10 days into aggregation cultures (AgC), it was shown that NR cells are "transdetermined" into lens direction, before the phenotypic expression of lens in cells at such earlier stages of SpC. In the second part of this article, we showed that NR-cells which have already expressed some neuronal phenotypes can transdifferentiate into lens. This statement is based upon the results of chimeric cultures consisting of neuronal cell fraction separated from 10-day SpC of quail NR and of the epithelial cell fraction of SpC of chick NR. Lens cells formed in such chimeric cultures were mainly of quail origin.

Animals↗
PubMedDate not supplied

[An analysis of keratin expression in the cells of the retinal pigment epithelium during transdifferentiation in newts].

Keratins of the cytoskeletal intermediate filaments have been identified immunohistochemically in pigment epithelium cells of the adult newt retina. We studied the expression of keratins in transdifferentiating and redifferentiating cells of the retinal pigment epithelium at different periods after removal of the retina. We have shown that the expression of keratins decreases. This appears as the decreased intensity of the immunospecific reaction soon after the operation. The latter observation has also been made immediately after artificial dissociation of the pigment epithelium cells of the retina isolated from nonoperated newt eyes. We found that the immunostaining of keratins was absent in the cells of normal and regenerating retina, as well as in retinal pigment epithelium cells before restoration of their structural and functional relationship with the retinal regenerate. The results obtained provide evidence for the inhibition of keratins expression during the transformation of retinal pigment epithelium into the retina. We proposed that there exists a mechanism responsible for gradual replacement of keratins by proteins of neurofilaments that have earlier been identified at the beginning of transdifferentiation of the retinal pigment epithelium.

Animals↗
PubMed1994

The loss of gap junctional cell-to-cell communication is coupled with dedifferentiation of retinal pigmented epithelial cells in the course of transdifferentiation into the lens.

Retinal pigmented epithelial cells (PECs) of the chick embryo can be cultured as a monolayer of melanized hexagonal cells. Modifications of the culture condition make the cells lose most of the phenotypes and further transdifferentiate into lentoid bodies within a few weeks. Ultrastructural observations showed that PECs and the lentoids have gap junctions with distinct morphology. Diffusion of a fluorescent dye confirmed the presence of gap junctions in both phenotypes. However, cells in the intermediate stage of transdifferentiation, which show neither the phenotype of the PEC nor that of the lentoid and are called dedifferentiated PECs here, have almost no gap junction structure. We propose the possibility that the dedifferentiation of PECs and the loss of cell-to-cell communication are tightly coupled events. This cell culture system is a suitable material for further studying this relationship by cellular and molecular approaches.

Animals↗
PubMed1993

In vitro growth and differentiation of rabbit bulbar, fornix, and palpebral conjunctival epithelia. Implications on conjunctival epithelial transdifferentiation and stem cells.

PURPOSE: The anterior surface of the eye is covered by several physically contiguous but histologically distinguishable epithelial overlying the cornea, limbus, bulbar conjunctiva, fornix conjunctiva, and palpebral conjunctiva. It is important to determine whether the different phenotypes of these epithelia are the result of intrinsic divergence, extrinsic modulation, or a combination of both. Based on keratin expression and cell kinetic criteria, the authors previously suggested that corneal epithelial stem cells may actually reside in the limbal basal layer. METHODS: In this article, the relationship between the corneal-limbal epithelial cells and conjunctival epithelial cells was analyzed by comparing their growth and differentiation properties in an identical cell culture environment. RESULTS: Using Dispase instead of trypsin to dissociate the cells, the authors were able to grow all five rabbit ocular surface epithelia in the presence of 3T3 feeder cells. They found that corneal and limbal cells synthesize identical keratins, including large amounts of the K3 and K12 markers of corneal-type differentiation. By contrast, all three conjunctival epithelia shared another keratin pattern, with large amounts of simple epithelial keratins but only minute amounts of K3/K12 keratins. CONCLUSIONS: This observation, coupled with previous findings that the "transdifferentiation" of conjunctival epithelial cells to corneal epithelium appears to be both incomplete and reversible, provides strong evidence that (1) the limbal-corneal epithelial cells form a lineage distinct from the conjunctival lineage and (2) conjunctival transdifferentiation actually represents a process of environmental modulation. In addition, of the three types of conjunctival epithelial cells, fornix cells were found to have a much greater proliferative potential than bulbar and palpebral cells. This observation, coupled with recent finding that fornix is enriched in slow-cycling (label-retaining) cells, raises the possibility that conjunctival epithelial stem cells may preferentially reside in the fornix.

Animals↗
PubMed1998

Epithelial-mesenchymal transdifferentiation and extracellular matrix gene expression in pleomorphic adenomas of the parotid salivary gland.

Mesenchymal and epithelial cell differentiation are assumed to be dichotomic primary events in embryonic development. In this study, pleomorphic adenomas of the parotid gland were analysed as a model which shows morphological features of both epithelial and mesenchymal tissue types. Using matrix gene expression profiles as a supplementary criterion for the identification of cellular phenotypes, areas with unequivocal epithelial and mesenchymal differentiation could be demonstrated. Many areas displayed a transitional phenotype with cells showing both epithelial and mesenchymal features. The data provide evidence that epithelial-mesenchymal transitions represent the basic principle of the tisuse heterogeneity in pleomorphic adenomas. Thus, pleomorphic adenomas demonstrate the potential of adult (neoplastic) epithelial cells to transdifferentiate into mesenchymal cells in vivo.

Adenoma, Pleomorphic↗
PubMed1997

Transforming growth factor-beta3 regulates transdifferentiation of medial edge epithelium during palatal fusion and associated degradation of the basement membrane.

Studies on transforming growth factor beta3 (TGF-beta3) deficient mice have shown that TGF-beta3 plays a critical role in palatogenesis. These null mutant mice have clefting of the secondary palate, caused by a defect in the process of fusion of the palatal shelves. A critical step in mammalian palatal fusion is removal of the medial edge epithelial cells from the midline seam and formation of continuous mesenchyme. To determine in more detail the role of TGF-beta3 in palatogenesis, we cultured TGF-beta3 null mutant and wild-type control palatal shelves in an organ culture system. The fate of the medial edge epithelial cells was studied in vitro using vital cell labeling and immunohistochemical techniques. Despite clear adherence, the null mutant palatal shelves did not fuse in vitro, but instead the medial edge epithelial cells survived at the midline position, and the basement membrane was resistant towards degradation. Supplementation of the culture medium with the mature form of TGF-beta3 was able to fully correct the defective fusion in the null mutant specimens. Our results demonstrate that the reason for the defective palatal fusion in TGF-beta3 (-/-) samples is not impaired adhesion. Our data define a specific role for TGF-beta3 in the events that control transdifferentiation of the medial edge epithelial cells including degradation of the underlying basement membrane.

Animals↗
PubMed2003

Stem cell plasticity, cell fusion, and transdifferentiation.

One of the most contentious issues in biology today concerns the existence of stem cell plasticity. The term "plasticity" refers to the capacity of tissue-derived stem cells to exhibit a phenotypic potential that extends beyond the differentiated cell phenotypes of their resident tissue. Although evidence of stem cell plasticity has been reported by multiple laboratories, other scientists have not found the data persuasive and have remained skeptical about these new findings. This review will provide an overview of the stem cell plasticity controversy. We will examine many of the major objections that have been made to challenge the stem cell plasticity data. This controversy will be placed in the context of the traditional view of stem cell potential and cell phenotypic diversification. What the implications of cell plasticity are, and how its existence may modulate our present understanding of stem cell biology, will be explored. In addition, we will examine a topic that is usually not included within a discussion of stem cell biology--the direct conversion of one differentiated cell type into another. We believe that these observations on the transdifferentiation of differentiated cells have direct bearing on the issue of stem cell plasticity, and may provide insights into how cell phenotypic diversification is realized in the adult and into the origin of cell phenotypes during evolution.

Animals↗
PubMed2004

Early regeneration genes: Building a molecular profile for shared expression in cornea-lens transdifferentiation and hindlimb regeneration in Xenopus laevis.

Recent studies in Xenopus laevis have begun to compare gene expression during regeneration with that of the original development of specific structures (e.g., the hindlimb and lens), while other studies have sought differences in gene expression between regeneration-competent and regeneration-incompetent stages. To determine whether there are any similarities between the regeneration of different structures, we have used a differential screen to seek shared early gene expression between hindlimb regeneration and cornea-lens transdifferentiation in the Xenopus tadpole. We have isolated 13 clones representing genes whose expression is up-regulated within the first few days of both regenerating processes and which are not demonstrably up-regulated in the context of basic wound healing. Furthermore, all of these genes also show prominent late embryonic expression. The expression patterns and putative identities of all 13 genes are presented, and a model is considered that allows us to characterize and profile important changes in gene expression, which might be shared among various regenerating and developmental systems.

Animals↗
PubMed2005

Experimental analysis of the transdifferentiation of visceral to parietal endoderm in the mouse.

The visceral endoderm (VE) of isolated extraembryonic regions (ExEmbs) of 7 days postcoitum (dpc) prestreak mouse conceptuses have been shown to convert readily to parietal endoderm (PE). The present study addresses the following three unanswered questions. On what does conversion depend, how rapidly does it occur, and is it an enduring general property of a residual small population of relatively immature cells? In situ hybridization reveals that change in cell state occurs within 2 days of culture. Deprivation of the mesoderm also promotes it in later ExEmbs. Conversely, the conversion to PE in isolated 7 dpc ExEmbs is suppressed by grafting 8 dpc or 9 dpc mesoderm. Hence, the conversion provides an example of transdifferentiation that is promoted by the absence of extraembryonic mesoderm. The presence of mesoderm seems to be necessary to enable the VE to grow rather than convert to PE, as occurs if it retains contact with the extraembryonic ectoderm.

Animals↗
PubMed2003

Skeletal myogenesis in the mouse esophagus does not occur through transdifferentiation.

To determine the developmental history of murine esophageal skeletal muscle, smooth muscle cells were fate mapped by lineage-specific recombination and phenotypically marked by eGFP. Examination of embryonic and postnatal tissues revealed that esophageal skeletal muscle does not arise from transdifferentiation of committed smooth muscle cells.

Animals↗
PubMed2005

Pigmented epithelium to retinal transdifferentiation and Pax6 expression in larval Xenopus laevis.

This study examines the retinal transdifferentiation (TD) of retinal pigmented epithelium (RPE) fragments dissected from Xenopus laevis larvae and implanted into the vitreous chamber of non-lentectomized host eyes. In these experimental conditions, most RPE implants transformed into polarized vesicles in which the side adjacent to the lens maintained the RPE phenotype, while the side adjacent to the host retina transformed into a laminar retina with the photoreceptor layer facing the cavity of the vesicle and with the ganglionar cell layer facing the host retina. The formation of a new retina with a laminar organization is the result of depigmentation, proliferation and differentiation of progenitor cells under the influence of inductive factors from the host retina. The phases of the TD process were followed using BrdU labelling as a marker of the proliferation phase and using a monoclonal antibody (mAbHP1) as a definitive indicator of retina formation. Pigmented RPE cells do not express Pax6. In the early phase of RPE to retinal TD, all depigmented and proliferating progenitor cells expressed Pax6. Changes in the Pax6 expression pattern became apparent in the early phase of differentiation, when Pax6 expression decreased in the presumptive outer nuclear layer (ONL) of the new-forming retina. Finally, during the late differentiation phase, the ONL, which contains photoreceptors, no longer expressed Pax6, Pax6 expression being confined to the ganglion cell layer and the inner nuclear layer. These results indicate that Pax6 may have different roles during the different phases of RPE to retinal TD, acting as an early retinal determinant and later directing progenitor cell fate.

Animals↗
PubMed2004

Direct transdifferentiation gives rise to the earliest new hair cells in regenerating avian auditory epithelium.

The avian auditory epithelium is capable of complete regeneration after hair cell (HC) loss. Most new HCs arise via cell division, but approximately one-third of new HCs arise via direct transdifferentiation (DT), in which supporting cells (SCs) alter their phenotype without dividing. In this study, we used synchronous, gentamicin-induced near-total HC loss in the basal end of the epithelium and continuous infusion of the cell division marker bromodeoxyuridine (BrdU) to identify the origin of each individual regenerating HC. Early new HCs were identified by immunolabeling for the HC-specific marker myosin-VIIa, and mitotic cells with BrdU immunolabeling. The first new HCs arising via DT appear 72-96 hr after gentamicin, 24-48 hr earlier than the first new mitotic HCs. After Day 6, however, most new HCs are mitotic. The "intermediate" morphology that has been suggested to be characteristic of DT is seen in HCs arising via both pathways. These findings suggest that DT is a simpler, more rapid process that produces the first new HCs, and that mitotic regeneration is somewhat slower but ultimately produces most new HCs. The identical morphology of regenerating HCs from both pathways suggests that once HC fate is established, all new HCs follow similar cellular processes during differentiation and reorganization into the regenerated epithelium.

Animals↗