Showing papers on "Cellular differentiation published in 1971"

Hemoglobin synthesis in murine virus-induced leukemic cells in vitro: stimulation of erythroid differentiation by dimethyl sulfoxide.

Abstract: Cells of a cloned line of murine virus-induced erythroleukemia were stimulated to differentiate along the erythroid pathway by dimethyl sulfoxide at concentrations that did not inhibit growth. A rise in the number of benzidine-positive normoblasts was accompanied by increased synthesis of heme and hemoglobin and a decrease in the malignancy of the cells. This action of dimethyl sulfoxide, which was reversible, may represent the derepression of leukemic cells to permit their maturation.

Morphologic differentiation of mouse neuroblastoma cells induced in vitro by dibutyryl adenosine 3':5'-cyclic monophosphate.

Abstract: The mechanism of mammalian neural differentiation is still obscure; but the availability of mouse neuroblastoma cells in vitro provides an opportunity to study some possible inducers of differentiation and this may help to elucidate the events involved at the molecular level. We have reported1 that X-irradiation of mouse neuroblastoma cells in vitro induces the formation of axons. The differentiated cells seem to undergo maturation: the soma and nucleus increase in size and the cytoplasm becomes granular. Here we report that N6O2 dibutyryl adenosine 3′:5′-cyclic monophosphate (dibutyryl cyclic AMP) induces axon formation in mouse neuroblastoma cells in vitro.

Differentiation of malignant to benign cells.

Abstract: Summary Rats bearing well-differentiated transplantable squamous cell carcinomas were given injections of thymidine-3H, and the tumors were examined at intervals of time by radioautography with light and electron microscopes. Two hr after injection, labeled cells were almost exclusively in the undifferentiated areas of the tumor, and 96 hr after injection many cells of the well-differentiated pearls were labeled. These data suggest that the growth of the tumor was dependent upon proliferation of undifferentiated cells and that the growth of the pearls was dependent upon incorporation of undifferentiated cells into the pearl. Labeled cells that migrated into the pearls became well differentiated, as determined by electron microscopic radioautography, and when transplanted into compatible hosts did not form tumors. Thus it would appear that the progeny of malignant stem cells can differentiate into postmitotic benign cells incapable of forming a tumor.

Determination of blastoderm cells in Drosophila melanogaster.

Abstract: A method for culturing blastoderm cells of Drosophila in vivo has been developed that allows these cells to differentiate into larval or adult structures By intermixture of genetically marked cells from bisected and whole embryos, it was shown that blastoderm cells are restricted in their potential for forming adult epidermal structures Cells isolated from anterior-half embryos are determined for forming head and thoracic structures, whereas cells from posterior-half embryos are determined for forming thoracic and abdominal structures The specificity of determination and the localization of determinative factors is discussed

Expression of differentiated functions in mouse neuroblastoma mediated by dibutyryl-cyclic adenosine monophosphate.

Abstract: CELLS derived from the mouse neuroblastoma (C1300) grown in culture are predominantly round and highly refractile. A small number of the cells are flatter and possess one or more extensions (“neurites”) which may be as long as 3 mm1–3. The proportion of these morphologically differentiated cells increases when the medium lacks serum4 or when 5-bromo-deoxyuridine is added5. The cells also contain enzymes of neural function2,6 and are capable of generating action potentials in vitro7,8. We now show that differentiated characteris-tics of neuroblastoma cells can be induced by N6,O2′-dibutyryl adenosine 3′ : 5′-monophosphate (dibutyryl-cyclicAMP).

Autoradiographic and ultrastructural observations on the frog's olfactory mucosa

Abstract: Autoradiographic techniques have been employed to study the cell turnover in the olfactory mucosa of frog. It has been established that basal cells of the olfactory epithelium divide and differentiate into mature neurons in adult animals. These findings prove that the olfactory neurons are replaced during the adult life. Supporting cells were also found to undergo turnover. The basal cells are indicated as the stem elements of both supporting and sensory cells as they undergo division and maturation processes leading to the replacement of both supporting and sensory cells.

Further Changes in Differentiation State Accompanying the Conversion of Chinese Hamster Cells to Fibroblastic Form by Dibutyryl Adenosine Cyclic 3′:5′-Monophosphate and Hormones

Abstract: The morphological conversion in vitro of Chinese hamster ovary cells to a fibroblast form by a relatively large amount of dibutyryl adenosine cyclic 3′:5′-monophosphate, or by a combination of small amounts of this compound and testosterone, is attended by appearance of the following additional properties: acquisition of strict contact inhibition of growth; reorientation of the random growth pattern into one in which cells grow parallel to their long dimension; disappearance of the randomly distributed, knob-like, pseudopodal structures around the cell periphery; induction of collagen synthesis; and decrease in the ability to be agglutinated and rounded up by plant agglutinins and specific cell antibodies. The changes in these characteristics are consistent with the conversion from a malignant to a normal fibroblastic state. This conversion is under genetic control, as demonstrated by the production of specific mutants with altered characteristics. The response to testosterone is specific since steroids like estradiol and hydrocortisone are inactive, and others have limited activity. Some prostaglandins are equal in activity to testosterone and 5α-dihydrotestosterone. This system appears useful in study of the regulation of phenotypic expression in mammalian cells.

Genes for neuronal properties expressed in neuroblastoma x L cell hybrids.

Abstract: Neuroblastoma cells with electrically excitable membranes were fused with electrically passive L cells having a hitherto undescribed electrical marker. Hybrid cells, examined 10-40 generations after fusion, were found to be electrically excitable. The results show that at least a part of the genetic information for neuron differentiation can be functionally expressed in N × L hybrid cells. Evidence for the regulation of action potential components was also found.

Genetic analysis of cell heredity in imaginal discs of Drosophila melanogaster.

Abstract: Somatic crossing-over was used in heterozygous Drosophila melanogaster to effect clonal homozygosity for three mutants (h, Hw, ac) In these mutants, one type of process, chaetae, replaces another type, trichomes, in specific patterns on the adult fly Heterozygous individuals were irradiated at different larval or pupal ages with x-rays and the somatic crossing-over was identified in the adult cuticle by genetically coupled mutants serving as cell markers of chaetae and trichomes Induction of homozygosis more than 8 hr before puparium formation resulted in autonomous differentiation of the mutant pattern in the homozygous patch of tissue for the three mutants tested; homozygosis induced within 8 hr of puparium formation was not followed by expression of the corresponding genotype 8 hr before puparium formation, each cell type still has to divide twice before metamorphosis and differentiation Thus, the genetically conditioned decision of a specific cell to differentiate either a chaeta or a trichome is made during the growth of the wing imaginal disc and is transmitted clonally to descendant cells Once this decision has been made, subsequent changes in the genotype of the cell or of its daughters are not material to the fate of the cell We introduce the term “perdurance” to designate the persistence of a cellular developmental fate for several cell generations after the loss of the genetic basis for that cellular development

Proliferation and differentiation of lymphoid cells: studies with human lymphoid cell lines and immunoglobulin synthesis

Abstract: Lymphoid cell regulation, especially in proliferation and differentiation, has been investigated by taking advantage of the unique opportunities presented by human lymphoid cells in tissue culture. This account of the major features of lymphoid cell proliferation and differentiation is organized to bring out features of the immune response in vivo that are paralleled by the behavior of lymphoid cell cultures in vitro. Evidence is presented to support the view that these cell lines are derived from normal human lymphoid cells which are representative of relatively immature but immunoglobulin committed cells. Finally, recent studies of the control of differentiation (immunoglobulin production) and proliferation of lymhoid cells are presented and discussed in the context of cell regulation and gene expression.

Differentiation and cancer.

Abstract: Cancer is discussed from a standpoint of a postembryonic differentiation. A differentiation requires the interaction of an exogenous inductive stimulus with competent precursor cell, which then evolve a new tissue with unique, stable heritable properties distinguishable from the progenitor. Evidence is cited pinpointing the normal stem cells of tissues as the competent target precursor cells in carcinogenesis. The resultant phenotype differs from its progenitor and has stable and unique characteristics. All of the characteristics associated with malignancy are expressed during some stage of development, suggesting that the normal genome contains the information necessary for malignant expression, and that the mechanism of malignancy is probably an alteration of control of genomic expression. Malignant tissue, like normal tissue, maintains itself by proliferation and differentiation of its stem cells; at least, that is what was observed in two tumors examined. In each of these tumors the differentiated progeny of the malignant stem cells proved to be benign. A third tumor was adapted to growth in vitro and under the conditions of the experiments could be modulated by altering the in vitro conditions. These data suggest that direction of the naturally occurring differentiation that occurs in tumors may be a suitable therapeutic alternative to cytotoxic chemotherapy.

DNA synthesis in differentiating skeletal muscle cells: initiation by ultraviolet light.

Abstract: As skeletal muscle cells differentiate, they fail to initiate DNA synthesis. This rigid regulation, which persists even after cells are fully developed, does not extend to "repair" DNA synthesis, in that ultraviolet light initiates DNA synthesis in 99 percent of the muscle nuclei exposed. The rate of "repair" DNA synthesis in these nuclei, however, drops over 50 percent at the time of cell differentiation.

Nucleic acid metabolism in proliferating and differentiating colonic cells of man and in neoplastic lesions of the colon.

Abstract: Enzymes involved in the metabolism of nucleic acid precursors were assayed in proliferating and maturing cells in the colon of man and in cells removed from polypoid lesions of the colon. Cells were separated from superficial and deeper layers of colonic mucosa by a recently developed tissue-planing instrument. Gradients of thymidine kinase, thymidine phosphorylase, and adenine and hypoxanthine phosphoribosyltransferase activities were found to characterize different stages of cell differentiation in normal colon. Thymidine kinase and phosphorylase were highest in young, proliferating cells and decreased during differentiation and migration of the cells to the mucosal surface. Phosphoribosyltransferase activities were lowest in young, proliferating cells and increased during cell differentiation. In the polypoid lesions including carcinomas patterns of enzyme activity characterizing young, proliferative cells were found.

Quantitative changes in unscheduled DNA synthesis in rat muscle cells after differentiation.

Abstract: THE incorporation of tritiated thymidine (3H-thymidine) into cells not engaged in normal DNA replication has been called unscheduled DNA synthesis1. The phenomenon has been observed after X-irradiation1, ultraviolet irradiation2 and after exposure to the monofunctional alkylating agent methyl methane sulphonate3 (MMS) and other carcinogens4. In all published reports the cells showing unscheduled DNA synthesis had retained their proliferative capacity (and hence at least their potential ability to synthesize DNA). We have investigated whether differentiated cells—that is, cells which presumably will never have to initiate normal DNA synthesis—are still capable of unscheduled DNA synthesis. We used multinucleated rat muscle cells in vitro. Myotubes have been found to form by fusion of separate, mononucleated cells5,6, the nuclei of which no longer synthesize DNA. YalTe and Gershon7 have shown that such cells can reinitiate DNA synthesis after viral infection. They found it necessary, however, for fusion to continue during viral infection; in the absence of further fusion no new DNA synthesis was observed. The trigger for DNA synthesis after viral infection must therefore have come from cells which had been transformed before differentiation and fusion. This left open the question of whether differentiated cells could initiate DNA synthesis in the absence of trigger from transformed cells.

Developmental changes of erythropoiesis in cultured chick blastoderms

Abstract: The erythropoietic area of very early chick embryos was cultured as a tissue for up to nine days to study the changes in red cell type and hemoglobin type, the cell cycle time, the cell population kinetics, and the DNA synthetase activity of these cells. It was found that the area vasculosa without the participation of the embryo proper contained the information and the timing mechanism required to produce not only the early primitive erythroid cell population, but also in due course, the later definitive cell type, each with its appropriate hemoglobin types. Also the precursors of the definitive cell type are active in DNA synthesis and therefore are probably in cycle very early in the culture period.

Regulation of gene expression in somatic cell hybrids: A review

Abstract: Hybridization of somatic mammahan cells in vitro was first observed in 1960 (1), at a time when experiments on the control of enzyme synthesis in bacteria were demonstrating the importance of recombinational systems for the analysis of genetic regulatory mechanisms (2). The discovery of ~ recombinational system for mammalian cells therefore suggested a new approach to the investigation of the mechanisms of the regulation of gene expression in these cells. This approach involves the combination in a hybrid of the genomes of two cells which differ in various functions and the analysis of the mechanisms underlying the differences in terms of interactions between the genomes in the hybrids. Analyses of this type have been performed on hybrids between cells of different species, between differentiated and undifferentiated cells, and between mutant and normal cells. The results of hybridizing cells in such combinations are described in this review.

Development and chromosomal constitution of nuclear-transplants derived from male germ cells.

Abstract: Nuclei of spermatogonial cells derived from juvenile and adult (Rana pipiens) were transplanted singly into enucleated eggs to determine whether germ cell nuclei are developmentally totipotent. Control nuclear transfers from undetermined somatic cells promoted genuine cleavage in 77% of the injected eggs and 54% of the complete blastulae derived from this series developed into normal larvae. In contrast to the control study, eggs transplanted with germ cell nuclei formed genuine blastulae in 13% of the cases, and most of the complete blastulae arrested before completing gastrulation. However, three embryos derived from adult germ cell nuclei did attain advanced stages of organogenesis and one of these developed into an abnormal feeding larva. These individuals are the most advanced nuclear-transplants obtained so far from nuclei of normal adult cells in vivo. Chromosome analyses performed on a sample of nuclear-transplants derived from germ cells revealed gross chromosomal abnormalities in all individuals except the larva. It is concluded, that even though germ cell nuclei are genetically totipotent, they, like somatic nuclei, undergo developmental restrictions during their process of cell differentiation, and after transplantation to host eggs, give rise to abnormal nuclear-transplants accompanied in most cases by karyotypic alterations. The significance of the developmental restrictions observed in germ cell nuclei is interpreted as an expression of chromosomal differentiation.

Cellular Interactions in the Regulation of Development in Annelids and Molluscs

Abstract: Publisher Summary This chapter presents an evaluation of the regulatory mechanisms, which form the basis for the development of the spiralian organism, its organs and organ systems, its tissues and cells, and its molecular specificity. The significance of the larval form lies in its adaptability to the environment and its role in evolution. The form of the larva can be understood by analysis of the organs present and through comparison of the presumptive areas. The theory of variable gene activity is being subjected to a critical analysis in spiralians, as in other organisms. This theory expresses the concept that a portion of the cell's genome functions at any particular time and that the active portion differs between different cell types. The activation of specific genes is a result of the cytoplasmic niche in which a particular nucleus finds itself. That niche quality is because of molecular configurations established in oogenesis and through the interactions of cells and tissues in the developing embryo. Fertilization, which forms the basis for embryogenesis and the establishment of diploidy, is one of the major cellular interactions and plays a significant role in the reorganization of the cytoplasm of the egg and the initiation of metabolic changes.

Regulation of the Synthesis of Choline-O-Acetyltransferase and Thymidylate Synthetase in Mouse Neuroblastoma in Cell Culture

Abstract: The specific activity of mouse neuroblastoma choline-O-acetyltransferase (EC 2.3.1.6.) increased 5.7-fold when the rate of cell division was restricted (as compared to cells kept rapidly dividing for 9 days); the specific activity of mouse neuroblastoma thymidylate synthetase increased 2.4-fold when nondividing cells again entered the logarithmic phase of cell growth. The highest specific activities for choline-O-acetyltransferase and lowest specific activities for thymidylate synthetase were obtained from cultures where cell division was restricted; the opposite result was observed when the cells were growing rapidly. Thus, the regulation of these two enzymes is out of phase with respect to each other and is dependent on the rate of cell division. The inverse relationship for the regulation of these two enzymes is discussed in relation to the needs of mitotic versus differentiated neuroblastoma cells.

Isoaccepting transfer RNA's in mammalian differentiated cells and tumor tissues.

Abstract: amino acids derived from the MOPC 31C plasma cell tumor and resolved by the RPC-2 column chromatography was published (28). Except for tryptophan, multiple peaks of isoaccepting tRNA were observed for each of the other 19 amino acids, each having its characteristic elution pattern. As compared to E. coli studied under similar Chromatographie conditions (24), MOPC 31C plasma cell tumors showed very different elution patterns of isoaccepting tRNA's for every

The human fetal synovium. Histology, fine structure and changes in organ culture.

Abstract: Fetal synovial tissues were obtained postmortem and maintained in organ culture. Preservation and morphologic differentiation was followed histologically for 2–4 weeks. The lining cells of the fetal synovium was found to consist of three cell types: fibroblasts, macrophages and undifferentiated cells. In culture the undifferentiated cells disappeared and the typical macrophages became scarce. Other changes observed were an apparent increase in mast cells, an intracellular accumulation of lipid inclusions, dilated endoplasmic reticulum, and intracellular collagen fibers.