Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Transdifferentiation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources
PubMed1999

Blockade of kit signaling induces transdifferentiation of interstitial cells of cajal to a smooth muscle phenotype.

BACKGROUND & AIMS: Interstitial cells of Cajal (ICC) serve as pacemaker cells and mediators of neurotransmission from the enteric nervous system to gastrointestinal muscles. ICC develop from mesenchymal cells that express c-Kit, and signaling via Kit receptors is necessary for normal development of ICC. We studied the fate of functionally developed ICC after blockade of Kit receptors to determine whether ICC undergo cell death or whether the phenotype of the cells is modified. The fate of undeveloped ICC was also investigated. METHODS: Neutralizing, anti-Kit monoclonal antibody (ACK2) was administered to mice for 8 days after birth. ICC in the small intestine were examined by immunohistochemistry and electron microscopy. Occurrence of apoptosis was also assayed. RESULTS: When Kit receptors were blocked, ICC nearly disappeared from the small intestine. Apoptosis was not detected in regions where ICC are normally distributed. Remaining Kit-immunopositive cells in the pacemaker region of the small intestine developed ultrastructural features similar to smooth muscle cells, including prominent filament bundles and expression of the muscle-specific intermediate filament protein, desmin, and smooth muscle myosin. ICC of the deep muscular plexus normally develop after birth in the mouse. Precursors of these cells remained in an undifferentiated state when Kit was blocked. CONCLUSIONS: These data, along with previous studies showing that ICC in the pacemaker region of the small intestine and longitudinal muscle cells develop from the same Kit-immunopositive precursor cells, suggest inherent plasticity between the ICC and smooth muscle cells that is regulated by Kit-dependent cell signaling.

Animals↗
PubMed1998

Studies of the neuronal transdifferentiation process in cultured human pheochromocytoma cells: effects of steroids with differing functional groups on catecholamine content and cell morphology.

The neuronal differentiation of adrenal pheochromocytoma cells from human subjects was studied in vitro for periods of up to 65 days. Changes with time in culture were observed in both intracellular catecholamine content (progressive decreases in epinephrine, norepinephrine, and dopamine, except for a possible transient early increase in the latter) and in morphology (increases in neurite outgrowth) of cells cultured in control medium; supplementation of cultures with nerve growth factor resulted in a substantial increase in neurite formation. The effects on these changes of the presence in the culture medium of various steroids were examined. The addition of 11-oxygenated steroids (aldosterone, corticosterone, cortisol, or dexamethasone) at 10(-5) M concentrations caused at least 2.5-fold increases in mean intracellular dopamine and norepinephrine levels; with dexamethasone, 9-10-fold increases were observed. Intracellular epinephrine content was also enhanced by 11,17-oxygenated steroids (dexamethasone and cortisol), but not by the other 11-oxygenated compounds studied. These two 11,17-oxygenated glucocorticoids also inhibited the morphologic changes seen with extended periods in culture, decreasing the outgrowth of neurite projections and causing cells to attain a vacuolated and granular appearance; the presence of dexamethasone strongly inhibited the morphologic changes induced by nerve growth factor. 11-Deoxy steroid intermediates (pregnenolone, 11-deoxycorticosterone, and 11-deoxycortisol) had little or no effect on catecholamine content or on morphology. Preliminary observations suggest that C-18 and C-19 sex steroid hormones (17 beta-estradiol and testosterone) may have morphologic effects opposite to those of the 11-oxygenated compounds, showing a slight stimulatory influence on the formation of neurite projections, but no significant effect on catecholamine content.

Adrenal Cortex Hormones↗
PubMed2002

Stabilization of beta-catenin induces lesions reminiscent of prostatic intraepithelial neoplasia, but terminal squamous transdifferentiation of other secretory epithelia.

The present study documents that stabilization of beta-catenin is sufficient to induce lesions reminiscent of prostate intraepithelial neoplasia (PIN). Such lesions were present in all compound mutant mice and all prostate acini expressing stabilized beta-catenin. High grade PIN-like lesions resembling early human prostate cancer were detected as early as 10 weeks of age. Surprisingly, stabilization of beta-catenin in other secretory epithelia including salivary, preputial, harderian, and mammary glands induced extensive squamous metaplasia and keratinization associated with terminal differentiation of the target cells, but failed to cause neoplastic transformation. Epidermal hyperplasia, hair follicle cysts, and odontomas were also observed. The prostatic lesions exhibited upregulation of c-myc, increased rate of cellular proliferation, loss of the Na-K-Cl co-transporter NKCC1, and expression of androgen receptor. Basal cell markers such as p63 and keratin 5 were not expressed by the masses of PIN-like lesions, but were present in small foci of proliferating beta-catenin expressing basal cells. Our observations indicate that beta-catenin stabilization is a crucial event for the initiation of PIN-like lesions, but induces squamous metaplasia rather than tumorigenesis in secretory epithelia other than the prostate.

Animals↗
PubMed2003

Interaction of leptin with gastric myofibroblast transdifferentiation in Helicobacter pylori-infected Mongolian gerbils: the effect of rebamipide.

BACKGROUND: Our recent histochemical studies have revealed the marked increase of myofibroblasts in the Helicobacter pylori-infected Mongolian gerbil fundic mucosa, while the mediators, which facilitate the conversion of fibroblasts to the myofibroblasts have remained unknown. AIM: The present study was undertaken to clarify the alteration of leptin in the control and H. pylori-infected Mongolian gerbil stomach. The effector sites of rebamipide were also investigated in relation to leptin. METHODS: The localization of leptin was investigated by the indirect immunofluorescence. Plasma leptin levels were determined by ELISA method. The localization of 3H-rebamipide binding sites was investigated by autoradiography. RESULTS: Serum leptin content in H. pylori-infected Mongolian gerbils was significantly increased. The presence of leptin immunoreactivity was recognized in the endothelial cells of the microcirculatory network and very weakly in the glandular cells in the control group, while in the H. pylori-infected group leptin was markedly recognized in the mesenchymal cells. Rebamipide bound to the fibroblasts and surface mucous cells and decreased the leptin immunoreactivity in the gastric mucosa. CONCLUSIONS: Leptin was mostly found in the mesenchymal cells. Rebamipide administration brought about the decrease of leptin in the gastric mucosaof the H. pylori-infected gerbils.

Alanine↗
PubMed2002

Expression of CCK2 receptors in the murine pancreas: proliferation, transdifferentiation of acinar cells, and neoplasia.

BACKGROUND & AIMS: To explore the pancreatic function of CCK2/gastrin receptor, we created ElasCCK2 transgenic mice expressing the human receptor in pancreatic exocrine cells. In previous studies, the transgenic CCK2/gastrin receptor was demonstrated to mediate enzyme release and protein synthesis. We now report results of phenotypic and long-term studies. METHODS: Pancreas was characterized using morphometry and immunohistochemistry. ElasCCK2 mice were crossed with INS-GAS mice expressing gastrin in pancreatic beta cells to achieve continuous stimulation of the CCK2/gastrin receptor. RESULTS: The pancreatic weight of ElasCCK2 mice was increased by 40% and correlated with an increase in the area of exocrine tissue. Alterations in pancreatic histology were apparent from postnatal day 50. Crossing the ElasCCK2 mice with INS-GAS mice resulted in development of morphologic changes in younger animals. Malignant transformation occurred in 3 of 20 homozygous ElasCCK2 mice. Although tumors had different phenotypes, they all developed through an acinar-ductal carcinoma sequence. CONCLUSIONS: Our data show that transgenic expression of a G protein-coupled receptor can lead to cancer. This study also supports a key role of the CCK2/gastrin receptor in the development of pre- and neoplastic lesions of the pancreas. ElasCCK2 mice provide a model for carcinogenesis by transformation and dedifferentiation of acinar cells.

Animals↗
PubMed2005

Transdifferentiation of corneal epithelium into epidermis occurs by means of a multistep process triggered by dermal developmental signals.

Differentiated cells of the corneal epithelium are converted to hair, along with their associated stem cells, then interfollicular epidermis, by means of a multistep process triggered by dermal developmental signals. The committed basal cells of the adult corneal epithelium dedifferentiate under the control of signals from an associated embryonic hair-forming dermis, likely Wnts, and revert to a limbal basal cell phenotype. This initial process involves the down-regulation of Pax6 and the loss of expression of corneal-specific keratins and the induction of basal keratinocyte markers. These dedifferentiated cells are able to reinduce dermal condensations, which in turn induce the formation of hair follicles from cells that have lost Pax6 expression, by means of a Noggin-dependent mechanism. An epidermis is subsequently formed by cells derived from the newly segregated hair stem cells.

Animals↗
PubMed2002

Development of gonadotropes may involve cyclic transdifferentiation of growth hormone cells.

The cyclic rise in expression of anterior pituitary gonadotropins coincides with the appearance of cells sharing gonadotropic and somatotropic phenotypes. To learn more about possible factors that regulate the origin of this cell type, we studied the time of appearance of cells that co-expressed growth hormone (GH) and gonadotropins and estrogen receptors during the estrous cycle and compared this timing with known changes in regulatory hormones or their receptors. The first event in this cell population is an increase in expression of estrogen receptor (ER)beta by GH cells from estrus to metestrus suggesting that estrogen may mediate this early change. Expression of GH mRNA rises rapidly from metestrus to mid-cycle. The rise is seen first in GH cells and then in cells with luteinizing hormone (LH) antigens. These data suggest that, early in the cycle, cells bearing GH and growth hormone releasing hormone (GHRH) receptors begin to produce LH and gonadotropin releasing hormone (GnRH) receptors. Early in proestrus, there is an increase in cells with GH and follicle-stimulating hormone (FSH) suggesting that this set of multipotential cells develops later than GH-LH cells. This fits with earlier studies showing the later rise in expression of FSH mRNA. Collectively these data suggest that the anterior pituitary contains a subset of GH cells that have the capacity to respond to multiple releasing hormones and support more than one system.

Activins↗