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Results for “differentiation”

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At least 19 recordsLinked to original sources

PubMed1976

Biogenesis of mitochondrial membranes in Neurospora crassa during cellular differentiation: ultrastructural changes accompanying differentiation.

The ultrastructural characteristics of Neurospora cells during dedifferentiation and redifferentiation of conidiospores into vegetative cells have been determined. This germination process occurs between 2 and 5 h after inoculation; by 3-5 h, approximately 50% of the cells have germinated. The cells enter the exponential phase of dry-weight gain between 4 and 5 h after inoculation. Several unusual structures are observed in Neurospora cells during germination. Whorled structures are frequently seen in the cytoplasm during germination, and occasionally at other times. They appear to be derived from the cytoplasmic membrane. Whorled structures of different appearance were observed in the mitochondria between 2 and 4 h after inoculation. Their number was related to the level of metabolizable carbohydrate, and was higher in 15% glucose-than in 2% sucrose-supplemented medium, and very low in medium containing 15% mannitol, or 2% sucrose+13% 2-deoxyglucose, or no added carbohydrate. The mitochondrial inclusions were osmiophilic and could be removed by treatment with 90% aqueous acetone in the cold, indicating that they were composed at least in part of lipid. The strong dependence of the number of mitochondrial inclusions on time and on carbohydrate supplementation, suggests that there is a physiological basis for these structures and that they reflect changes occurring in the mitochondria at times significant to cellular differentiation.

Carbohydrate Metabolism↗

PubMed1979

[Factors that control the differentiation of stem cells. I. The change in direction of hematopoietic stem cell differentiation under the effect of differentiating T-lymphocytes].

A mixed transplantation of bone marrow cells, and lymph nodes or thymic cells of mice CBA strain into lethally irradiated hybrid recipients (CBAXC57B1)F1 is accompanied with changes in the differentiation pattern from a mainly erythroid to a mainly granuloid way. Thymectomy of either donor of bone marrow cells or recipients, or both, destroys the stem cell differentiation in the direction of granulopoieseis. Intact syngeneic lymphocytes normalize differentiation of the stem cells, but in the presence of tissue antigens these provide for the stem cell differentiation mainly in the direction of granulopoiesis. The differentiation of stem haemopoietic cells is accomplished under the thymic and lymphocyte control. T-differentiating lymphocytes (Td) are the lymphocytes controlling the stem cell differentiation.

Animals↗

PubMed1979

Stem cell growth and differentiation in Hydra attenuata. II. Regulation of nerve and nematocyte differentiation in multiclone aggregates.

The differentiation of nerve cells and nematocytes from interstitial stem cells in Hydra has been investigated under conditions of changing stem cell density. Interstitial stem cells were cultured in a feeder layer system consisting of aggregates of nitrogen mustard-inactivated tissue. The aggregates were seeded with varying numbers of stem cells from 10 to 400 per aggregate; between 4 and 7 days later the rates of nerve and nematocyte differentiation were measured. Nerve differentiation was scored by labelling the stem cell population with [3H]-thymidine and counting nests of 4 proliferating nematoblasts. In both cases the numbers of differentiating cells were normalized to the size of the stem cell population. The results indicate that the rate of nematocyte differentiation increases as the concentration of stem cells increases in aggregates; under the same conditions the rate of nerve differentiation remains essentially constant. To calculate the numbers of stem cells entering each pathway per generation, a computer was programmed to simulate the growth and differentiation of interstitial stem cells. Standard curves were prepared from the simulations relating the rates of nerve and nematocyte differentiation to the fraction of stem cells committed to each pathway per generation. The rates of nerve and nematocyte commitment were then estimated from the experimentally observed rates of differentiation using the standard curves. The results indicate that nerve commitment remains constant at about 0.13 stem cells per generation over a wide range of stem cell concentration. Nematocyte commitment, by comparison, increases from 0.15 to 0.21 stem cells per generation as stem cell concentration increases in aggregates. The fact that the ratio of nerve to nematocyte commitment changes under our conditions suggests that stem cell commitment is not a stochastic process but subject to control by environmental stimuli.

Animals↗

PubMed1992

Induction by bufalin of differentiation of human leukemia cells HL60, U937, and ML1 toward macrophage/monocyte-like cells and its potent synergistic effect on the differentiation of human leukemia cells in combination with other inducers.

We have recently demonstrated that bufalin is a new potent inducer of the differentiation of human myeloid leukemia cells. The present work was carried out to examine further the effect of bufalin on the growth and characteristics of human leukemia-derived cell lines U937, ML1, and HL60. At concentrations of 5-10 nM, bufalin decreased the growth of ML1 cells preferentially at the G2 phase and U937 cells at the S and G2 phases of the cell cycle. Bufalin, under these conditions, induced the differentiation of U937, ML1, and HL60 cells to monocyte/macrophage-like cells by measuring the expression of various differentiation markers, as assessed by morphology and histochemistry, and ability to phagocytose latex particles, to reduce nitroblue tetrazolium, and to develop Fc receptors. U937 and ML1 cells started to differentiate at 4 and 6 h, respectively, after treatment with 10 nM bufalin and showed maximum differentiation 72 h later. At present, a mechanism for the bufalin-mediated induction of the differentiation of these human leukemia cells remains to be determined. The combination of bufalin with all-trans retinoic acid, 1 alpha,25-dihydroxyvitamin D3, 4'-demethylepipodophyllotoxin ethylidene-beta-D-glucoside (VP16), or human gamma-interferon synergistically induced the differentiation of HL60 and U937 cells. A similar effect on ML1 cells was observed with the combination of bufalin with VP16 or human rTNF-alpha. These results suggest that bufalin in combination with VP16, all-trans retinoic acid, 1 alpha,25-dihydroxyvitamin D3, rTNF-alpha, or gamma-interferon may be very useful in the differentiation of human leukemia.

Antineoplastic Agents↗

PubMed2025

A Study on Differential Proteomics in Differentiated Gastric Adenocarcinoma With Low-grade Atypia Based on Paraffin-embedded Tissues.

In this study, we analyzed and characterized differentially expressed proteins in differentiated gastric adenocarcinoma with low-grade atypia for screening potential protein markers. We collected gastric tissue specimens from 90 patients treated at the Pathology Department of the First People's Hospital of Yunnan Province, China, between January 2019 and December 2022. These specimens had been fixed in 10% neutral-buffered formalin and embedded in paraffin. We classified these samples into 3 groups: the control group (normal gastric mucosa), the low-grade atypia group (differentiated gastric adenocarcinoma with low-grade atypia), and the high-grade atypia group (differentiated gastric adenocarcinoma with high-grade atypia), consisting of 30 cases in each group. We analyzed differential proteomes with the data-independent acquisition-mass spectrometry (DIA-MS) methodology and selected 4 differentially expressed proteins that were subjected to immunohistochemistry (IHC) staining for validation. A total of 4406 proteins were identified, among which 598 and 357 proteins were statistically different in the low-grade atypia group as compared with the control group and the high-grade atypia group, respectively. IHC staining showed that the expression of FHL3, CSRP2, and FCGR3A was significantly higher in the low-grade atypia group than in the control group ( P <0.05) and significantly higher in the high-grade atypia group than in the low-grade atypia group ( P <0.05). FHL2 expression was negative to weakly positive in the control and low-grade atypia groups and not significantly different between the 2 groups, whereas FHL2 expression in the high-grade atypia group was significantly higher than in the control and low-grade atypia groups ( P <0.05). Proteomic analysis is helpful for discovering new protein markers. Using a combination of FHL3, CSRP2, and FCGR3A can increase the accuracy of the pathologic diagnosis of differentiated gastric adenocarcinoma with low-grade atypia.

Humans↗

PubMed1975

Control of normal differentiation of myeloid leukemic cells. VIII. Induction of differentiation to mature granulocytes in mass culture.

There are three types of myeloid leukemic cells, IR+D, IR+D- and IR-D-. IR+D+ cells were induced to differentiate to granulocytes in mass culture in liquid medium by conditioned medium (CM) from cultures of lungs from mice injected with endotoxin. About 90% of the leukemic cells were induced to differentiate, 50% to mature granulocytes and 40% to intermediate stages. An efficient induction of granulocyte differentiation was also obtained with CM from primary cultures of rat embryo or human spleen and there was a lower activity with CM from various other sources. IR+D- cells were induced to differentiate to about 20% cells with intermediate stages but not to mature granulocytes; IR-D- cells could not be induced to differentiate to intermediate or mature stages. IR+D+ cells were induced to form intermediate stages of granulocyte differentiation, to phagocytose and to attach to the surface of the Petri dish, three days after incubation with CM. Optimum induction of mature granulocytes required six more days incubation with CM. Mature granulocytes induced from leukemic cells showed cytochemical properties and a morphology in the electron microscope similar to that of normal mature granulocytes. These induced granulocytes did not form leukemiac in animals or colonies in agar. The granulocytes induced from the myeloid leukemic cells, therefore, behaved like normal mature granulocytes.

Acid Phosphatase↗

PubMed1976

Control of normal differentiation of myeloid leukemic cells. XI. Induction of a specific requirement for cell viability and growth during the differentiation of myeloid leukemic cells.

Normal hematopoetic cells require the presence of a protein (MGI) in the appropriate conditioned medium (CM) for cell viability and growth and for differentiation to mature macrophages and granulocytes. Clones of myeloid leukemic cells have been established in culture (D+ clones) which require CM with this protein for differentiation, but not for cell viability and growth. It has been shown that these leukemic cells can be induced by CM to again require, like normal cells, the presence of CM for cell viability and growth. Induction of this requirement, which will be referred to as RVG, occurred before the D+ cells differentiated to mature granulocytes. Clones of myeloid leukemic cells (D- clones) that could not be induced to differentiate to mature cells, did not show the induction of RVG. The steroid hormones prednisolone and dexamethasone can induce some, but not all the changes associated with differentiation of D+ cells, Incubation with these steroids did not result in the induction of a requirement for these steroids for cell growth and viability. Studies with CM from different sources have shown, that all batches that induced RVG also induced differentiation of D+ cells and that both activities were inhibited after treating the CM with trypsin. It is suggested that the same protein (MGI) may be involved in both activities. Incubation of D+ cells with CM resulted in an increase in agglutinability by concanavalin A and this increase was maintained even in the absence of CM. This suggests, that the induction of RVG in D+ myeloid leukemic cells is associated with a change in the cell surface membrane.

Agglutination↗

PubMed2025

Nfe2l1 dysfunction alters Parkinson's disease-related gene expression and impairs neuronal differentiation under ubiquitin stress in neuronal differentiated P19 Cells.

Proteostasis is essential for neuronal health, and its disruption is implicated in neurodegenerative diseases such as Parkinson's disease (PD). Nfe2l1, a key regulator of proteostasis and ubiquitination, plays a significant role in neuronal health, yet its molecular functions in neuronal cells remain unclear. Our study investigates the role of Nfe2l1 in RA-induced neuronal differentiation of P19 cells under proteasome inhibition. This condition significantly increased Nfe2l1 expression at both protein and RNA levels in wild-type and differentiated cells. In differentiated cells under proteasome inhibition, RNA sequencing revealed an enrichment of neurodegenerative pathways, particularly those associated with PD. Proteasome inhibition led to the upregulation of several PD-related genes, including Atf6, Camk2d, and Sod1. However, Nfe2l1 knockdown in differentiated cells significantly reduced the expression of these genes, highlighting the role of Nfe2l1 in the regulation of PD-related pathways. Knockdown of Nfe2l1 also decreased Neat1, a long non-coding RNA associated with PD pathology, and downregulated the neuronal marker Map2, indicating impaired neuronal differentiation. Furthermore, Nfe2l1 knockdown increased ubiquitination under proteasome inhibition, emphasizing its role in protein degradation and neuronal homeostasis under stress. These findings highlight Nfe2l1 as a critical regulator in neuronal cells and reveal its potential role in maintaining proteostasis and involvement in neurodegenerative disease mechanisms, such as PD.

Parkinson Disease↗

PubMed1978

Adaptive differentiation of murine lymphocytes. I. Both T and B lymphocytes differentiating in F1 transplanted to parental chimeras manifest preferential cooperative activity for partner lymphocytes derived from the same parental type corresponding to the chimeric host.

The concept of adaptive (selective) differentiation preducts that early differentiation of lymphocytes is conditioned by the environment in which such differentiation takes place. These processes appear to involve selection of lymphocytes according to their self-recognition between interacting lymphocytes is, at least in part, controlled by major histocompatibility complex-linked genes, then adaptive differentiation is also controlled by these genes. In these studies, we have tested the capacities of helper T lymphocytes and hapten-specific B lymphocytes primed in the environments of various combinations of bone marrow chimeras prepared between two parental strains (i.e. A/J and BALB/c) and their corresponding F1 hybrid (CAF1) to interact with primed B and T lymphocytes derived from conventional parent and F1 donors as well as all of the corresponding bone marrow chimera combinations. The results demonstrate clearly that (a) F1 transplanted to F1 chimeric lymphocytes display no restriction in terms of cooperative activity with all of the various partner cell combinations; (b) parent transplanted to F1 chimeric lymphocytes manifest effective cooperative activity only for partner cells from F) or parental donors corresponding to the haplotype of the original bone marrow donor, thereby behaving phenotypically just like conventional parental lymphocytes; and (c) F1 transplanted to parent chimeric lymphocytes display restricted haplotype preference in cooperating best with partner lymphocytes sharing the H-2 haplotype, either entirely or codomimantly, of the parental chimeric host. The implications of these findings for understanding certain controlling mechanisms for lymphocyte differentiation are discussed.

Animals↗

PubMed1975

Differential expression of alpha- and beta-globin genes during differentiation of cultured erythroleukemic cells.

Murine erythroleukemic cells induced to differentiate in vitro with dimethylsulfoxide provide a model for events involved in the regulated expression of the globin genes. Here we examine alpha- and beta-globin gene expression in such cells which contain no detectable globin RNA prior to induction. To quantitate alpha- and beta-globin RNAs in cellular RNA samples by molecular hybridization techniques, highly radioactive complementary DNAs were synthesized using mouse alpha- and beta-globin RNAs purified by formamide gel electrophoresis. Maximally induced erythroleukemic cells and mouse reticulocytes contain nearly equal relative amounts of alpha- and beta-globin RNA. During the period in which globin RNA accumulates in differentiating erythroleukemic cells, however, alpha- and beta-globin RNAs are not present in equivalent amounts. alphaRNA is present in substantial excess (alpha/beta ratio 3.7) early in induction, and the alpha/beta RNA ratio progressively approaches 1 as differentiation proceeds further. These observations directly suggest that the alpha- and beta-globin genes are differentially expressed during cellular differentiation and raise questions as to how relative expression of globin genes is controlled during normal development.

Animals↗

PubMed1975

Xenopus laevis cement gland as an experimental model for embryonic differentiation. I. In vitro stimulation of differentiation by ammonium chloride.

Ectoblastic cells explanted from the animal pole of young Xenopus laevis gastrulae have been cultured in vitro. When these cells were cultured for five days in standard salt solutions they formed atypical epidermis. When they were first submitted for 6 h to Holtfreter solution containing ammonium chloride and then transferred for five days in standard Barth's solution they underwent differentiation into typical cement gland tissue. The optimum concentration of ammonium chloride was 10 mM. Below and above this concentration the resulting cement glands had a smaller volume. The optimum duration for the initial stimulation with 10 mM ammonium chloride in Holtfreter solution was 6 h. Shorter stimulation times produced only small cement glands. Longer initial incubations in ammonium chloride resulted in progressive dissociation of the explants. To obtain the best differentiation into cement gland it appeared that the pH of the ammonium chloride solution should be between 7-5 and 7-7. When the stimulation is performed under these optimum conditions the cement gland measured after five days of culture accounts for 80-90 percent of the explanted tissue. This means that all or almost all of the competent superficial layer of the ectoblastic cells underwent differentiation into cement gland. No other differentiated tissue was observed in the explants. The cement gland is a very simple organ containing only one single cell type. The gland obtained under the described in vitro conditions is therefore proposed as an experimental model for biochemical studies on early embryonic differentiation.

Ammonium Chloride↗

PubMed1977

The effects of neuraminidase and galactose oxidase on murine lymphocytes. I. Evidence for the differential delivery of signal(s) leading to cell proliferation and the differentiation of cytotoxic T cells.

The sequential treatment of normal C57BL/6 mouse spleen cell populations with neuraminidase (NA) and galactose oxidase (GO) resulted in cell proliferation, but not in the differentiation of cytotoxic T cells. In contrast, C57BL/6 spleen cells derived from animals primed 5 to 8 months earlier with alloantigen (P815 mastocytoma cells of the DBA/2 strain) both proliferated and demonstrated T cell-mediated cytotoxicity after NAGO stimulation. T cells differentiating into cytotoxic cells after NAGO treatment demonstrated properties similar to alloantigen-specific 'memory' T cells. These were: 1) cytotoxicity developed only from 'primed' cell populations, 2) cytotoxicity developed within 24 hr after NAGO treatment, 3) DNA synthesis was not required for the differentiation of cytotoxic cells during the first 24 hr of culture but both DNA synthesis and cell proliferation were required for the cytotoxicity developing after 24 hr, and 4) all cytotoxicity induced by NAGO showed specificity for the priming alloantigen. It was found, furthermore, that cytotoxicity could be induced at much lower GO concentrations than needed for increased DNA synthesis. We interpret this finding as an indication that NAGO can differentially deliver two 'signals' to T lymphocytes: one leading to cell proliferation, the other causing the differentiation of memory T cells into cytotoxic effectors.

Animals↗

PubMed2026

Comprehensive analysis of differentially expressed mRNAs, lncRNAs, and miRNAs involved in ovarian differentiation and development in Qihe gibel carp (Carassius gibelio var. Qihe).

Qihe gibel carp (Carassius gibelio var. Qihe) exhibits diverse reproductive modes including gynogenesis and sexual reproduction, yet the molecular mechanisms of ovarian differentiation remain poorly understood. Ovarian tissues at 20, 30, and 60 days after hatching (dah), representing key stages covering early ovarian differentiation and primary oocyte growth, were subjected to whole-transcriptome sequencing. A total of 27,259 mRNAs, 2622 lncRNAs, and 2467 miRNAs were differentially expressed. Cell cycle, transcription, translation, and DNA replication pathways were significantly upregulated from 20 to 60 dah. Oocyte meiosis was enriched from 20 and 30 dah, whereas metabolic pathways (lipid, carbohydrate, and nucleotide metabolism) were enriched from 30 to 60 dah, indicating sequential progression from meiosis initiation to primary oocyte growth with nutrient synthesis. Hub lncRNAs and key ceRNA networks (e.g., MSTRG.28669.5-miR-221-ccnb2) were identified. This study provides the first comprehensive characterization of ncRNA-mediated regulation and ceRNA networks during ovarian development in Qihe gibel carp, establishing a foundation for understanding ovarian differentiation in this species.

Animals↗

PubMed1977

Inhibition of RNA and protein syntheses makes non-differentiating mouse myeloid leukemia cells sensitive to a factor(s) stimulating differentiation.

Treatment with ascitic fluid from animals bearing various tumors, can induce mouse myeloid leukemia line cells, M1, to differentiate in vitro into macrophages and granulocytes. Cells were isolated that were resistant to the ascitic fluid factor(s) stimulating differentiation (D-factor). The resistant cells became sensitive to the D-factor and differentiated after treatment with various inhibitors of RNA synthesis (actinomycin D, nogalamycin, chromomycin A3 or cordycepin) or protein synthesis (puromycin or cycloheximide). The cells could not be induced to differentiate by treatment with the inhibitors alone. The effective doses of the inhibitors of protein synthesis were toxic to the cells. Among these inhibitors actinomycin D (5 ng/ml) was the most effective for sensitizing the resistant cells. Inhibitors of DNA synthesis did not sensitize the resistant cells. Added actinomcyin D was mainly recovered in the nuclear fraction of the cells. The sensitizing effect of actinomycin D on the cells was roughly parallel to the extent of its inhibition of RNA synthesis in the cells. The effective concentration of actinomycin D (5 ng/ml) mainly inhibited it also inhibited alpha-amanitin-resistant RNA synthesis to some extent. These results suggest that alpha-amanitin-sensitive RNA synthesis may be involved in sensitization of the resistant cells to the D-factor.

Animals↗

PubMed1979

Actinomycin D restores in vivo sensitivity to differentiation induction of non-differentiating mouse myeloid leukemia cells.

Resistant mouse myeloid leukemia cells could not be induced to differentiate in vitro into mature macrophages and granulocytes by incubation with ascitic fluid or dexamethasone as inducer. Neither could endogenous inducers acting on resistant cells maintained in a diffusion chamber in syngeneic SL mice induce differentiation. However, when resistant cells were pretreated in vitro with low doses of actinomycin D they became sensitive to inducer in vitro or in vivo. The concentration of actinomycin D effective for this effect did not induce differentiation. The effect of actinomycin D was not due to inhibition of cell growth, since sensitivity was not observed when resistant cells were pretreated with the growth inhibitor 5-fluorodeoxyuridine. When resistant cells were kept in a diffusion chamber in mice injected with low doses of actinomycin D they showed significant differentiation, suggesting that the in vivo effect of actinomycin D is partly attributable to sensitization of the resistant cells to endogenous inducers.

Animals↗

PubMed1979

Human epidermal cell cultures: growth and differentiation in the absence of differentiation in the absence of dermal components or medium supplements.

Human epidermal cells grew and differentiated in vitro, provided that the pH of the culture medium was at 5.6-5.8, the seeding density was optimal (approximately 2.5 x 10(5) cells per cm2), and the incubation temperature was maintained at 35-37 degrees C. Under these conditions, epidermal cells from many different skin locations grew to confluency within 15-20 days and formed multi-layered sheets whose differentiated structure resembled that of the full depth of skin epidermis. Cell proliferation and differentiation did not require a feeder layer, a collagen substrate, a high concentration of fetal bovine serum, or added hormones. The sheets of differentiated epidermal cells could be dissociated from the plastic surfaces of the tissue culture flasks. The use of such cultured cells for wound dressing is proposed.

Cell Differentiation↗

PubMed1978

Control of normal differentiation of myeloid leukemic cells. XIII. Inducibility for some stages of differentiation by dimethylsulfoxide and its disassociation from inducibility by MGI.

There are clones of myeloid leukemic cells that can be induced to differentiate by the normal differentiation-inducing protein MGI to form Fc and C3 rosettes, mature macrophages and granulocytes. One of these clones (MGI+DMSO+) was also inducible by dimethylsulfoxide (DMSO) for C3 but not Fc rosettes, and for mature macrophages but not for mature granulocytes. Other clones (MGI+DMSO-) were inducible by MGI but not DMSO and a third type of clone (MGI-DMSO-) was not inducible by either compound. Clones that differed in their inducibility by DMSO showed a similar inhibition of cell multiplication by DMSO. The results indicate, that some stages of differentiation can be induced by DMSO in an appropriate clone of myeloid leukemic cells and that there are different cellular sites for induction by DMSO and MGI.

Cell Differentiation↗

PubMed1979

Inducers of mammalian cell differentiation stimulate dome formation in a differentiated kidney epithelial cell line (MDCK).

Cell cultures of a differentiated kidney epithelial cell line, MDCK, spontaneously form fluid-filled domes or hemicysts composed of numbers of cells as a manifestation of specialized epithelial transport phenomena. Addition to MDCK cells of a broad spectrum of compounds that are known as potent inducers of mammalian cell differentiation in cell culture caused a striking increase in the frequency of dome formation. Polar compounds such as N,N-dimethylformamide, dimethyl sulfoxide, or hexamethylene bisacetamide stimulated increased dome formation 15--30 hr after addition. Induction of domes by these compounds was prevented either by inhibitors of protein synthesis or by ouabain, cytochalasin B, or vinblastine. Inhibition of DNA synthesis did not block chemical induction of domes. Other inducers were compounds of physiological occurrence such as n-butyrate or adenosine. Furthermore, a variety of conditions expected to elevate intracellular levels of cyclic AMP also stimulated dome formation. These findings suggest the hypothesis that domes are formed in cell culture by a form of cell differentiation that is under positive control by cyclic AMP.

Acetamides↗