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At least 91 records · Page 5Linked to original sources
PubMed2004

Runx3-/- gastric epithelial cells differentiate into intestinal type cells.

We have previously reported that Runx3, a runt domain transcription factor, is a major growth regulator of gastric epithelial cells, that a lack of RUNX3 function is causally related to the genesis and progression of human gastric cancer, and that expression of RUNX3 is greatly reduced in intestinal metaplasias in human stomachs. Here we examined the differentiation of Runx3-/- mouse gastric epithelial cells and found that some cells differentiated into intestinal type cells, which expressed Cdx2, a transcription factor that has been shown to induce intestinal metaplasia in transgenic mice. Differentiation of intestinal type cells was not found in culture of Runx3+/+ gastric epithelial cells. These results suggest that gastric epithelial cells can differentiate into intestinal type cells, probably due to expression of Cdx2 in them when the function of Runx3 is impaired. The relationship between loss of function of Runx3, formation of intestinal metaplasia, and gastric cancer was discussed.

Animals↗
PubMed2001

A human breast epithelial cell type with stem cell characteristics as target cells for carcinogenesis.

Two types of human breast epithelial cells (HBEC) have been characterized. In contrast to Type II HBEC, which express basal epithelial cell phenotypes, Type I HBEC are deficient in gap junctional intercellular communication and are capable of anchorage-independent growth and of expressing luminal epithelial cell markers, estrogen receptors, and stem cell characteristics (i.e. the ability to differentiate into other cell types and to form budding/ductal organoids on Matrigel). A comparative study of these two types of cells has revealed a high susceptibility of Type I HBEC to immortalization by SV40 large T antigen, although both types of cells are equally capable of acquiring an extended life span (bypassing senescence) after transfection with SV40. The immortalization was accompanied by elevation of a low level of telomerase activity in the parental cells after mid-passage ( approximately 60 cumulative population doubling levels). Thus HBEC do have a low level of telomerase activity, and Type I HBEC with stem cell characteristics are more susceptible to telomerase activation and immortalization, a mechanism which might qualify them as target cells for breast carcinogenesis. The immortalized Type I HBEC can be converted to highly tumorigenic cells by further treatment with X rays (2 Gy x 2) and transfection with a mutated ERBB2 (also known as NEU) oncogene, resulting in the expression of p185(ERBB2) which is tyrosine phosphorylated.

Animals↗
PubMed1985

Clonal sublines of rat neurotumor RT4 and cell differentiation. V. Comparison of Na+ influx, Rb+ efflux, and action potential among stem-cell, neuronal, and glial cell types.

A multipotential stem-cell-type cell line (RT4-AC) isolated from a rat peripheral neurotumor differentiates in culture into two neuronal-type cells (RT4-B and RT4-E) or into a glial-type cell (RT4-D). The neuronal classification of RT4-B and RT4-E cells is based on their positive response to veratridine in the tetrodotoxin-sensitive Na+-influx and Rb+-efflux assays and on the action potential observed upon hyperpolarized stimulation. In addition, these neuronal cell types do not synthesize two glial proteins, S100 protein (S100P) and glial fibrillary acidic protein (GFAP). The glial classification of RT4-D is based on the syntheses of S100P and GFAP. Additionally, RT4-D does not display veratridine-activated Na+ influx and Rb+ efflux nor action potential. The stem cell type, RT4-AC, expresses both neuronal and glial properties to a lesser degree. In the neuronal-type cell lines of the RT4 family (RT4-B and RT4-E), the large veratridine-activated Na+ influx can further be stimulated by scorpion toxin. The Na+ influx of the stem cell (RT4-AC), however, is only slightly stimulated by veratridine alone, but greatly stimulated by the addition of veratridine and scorpion toxin. These observations suggest that a progressive differentiation of voltage-dependent Na+ channels may have occurred by the cell-type conversion from the stem cell type to the neuronal cell types. The exact nature of the change in Na+ channels is currently not known.

Action Potentials↗
PubMed1999

High susceptibility of a human breast epithelial cell type with stem cell characteristics to telomerase activation and immortalization.

We have recently characterized two types of normal human breast epithelial cells (HBECs) from reduction mammoplasty. Type I cells express estrogen receptor, luminal epithelial cell markers, and stem cell characteristics (i.e., the ability to differentiate into other cell types and to form budding/ductal structures on Matrigel), whereas Type II cells show basal epithelial cell phenotypes. In this study, we have examined whether Type I HBECs are more susceptible to telomerase activation and immortalization after transfection with SV40 large T-antigen. The results show that both types of cells acquire extended life span [(EL); i.e., bypassing senescence] at a comparable frequency. However, they differ significantly in the ability to become immortal in continuous culture, ie., 11 of 11 Type I EL clones became immortal compared with 1 of 10 Type II EL clones. Both parental Type I and Type II cells as well as their transformed EL clones at early passages [approximately 30 cumulative population doubling level (cpdl)] showed a low level of telomerase activity as measured by the telomeric repeat amplification protocol assay. For all 11 of the Type I EL clones and the single Type II EL clone that became immortal, telomerase activities were invariably activated at middle passages (approximately 60 cpdl) or late passages (approximately 100 cpdl). For the four Type II EL clones randomly selected from the nine Type II clones that did not become immortal, the telomerase activities were found to be further diminished at mid-passage, before the end of the life span. Thus, normal HBECs do have a low level of telomerase activity, and Type I HBECs with stem cell characteristics are more susceptible to telomerase activation and immortalization, a basis on which they may be major target cells for breast carcinogenesis.

Breast↗
PubMed2003

Fireworks in the primate retina: in vitro photodynamics reveals diverse LGN-projecting ganglion cell types.

Diverse cell types and parallel pathways are characteristic of the vertebrate nervous system, yet it remains a challenge to define the basic components of most neural structures. We describe a process termed retrograde photodynamics that allowed us to rapidly make the link between morphology, physiology, and connectivity for ganglion cells in the macaque retina that project to the lateral geniculate nucleus (LGN). Rhodamine dextran injected into the LGN was transported retrogradely and sequestered within the cytoplasm of ganglion cell bodies. Exposure of the retina to light in vitro liberated the tracer and allowed it to diffuse throughout the dendrites, revealing the cell's complete morphology. Eight previously unknown LGN-projecting cell types were identified. Cells could also be targeted in vitro for intracellular recording and physiological analysis. The photodynamic process was also observed in pyramidal cells in a rat neocortical slice.

Action Potentials↗
PubMed1988

A new assay for the measurement of the attachment of neutrophils and other cell types to endothelial cells.

A microassay for the detection of cellular adherence to monolayers of cultured human vascular endothelium has been developed that utilises the uptake by cells of the vital stain, Rose Bengal. Changes in the optical density as a result of increased attachment give an accurate measurement of the extent of cellular adherence. The assay utilises small numbers of endothelial cells to obtain confluent monolayers, is rapid (results available within 1.5 h from commencement), allows large numbers of investigations to be performed at the one time, eliminates the requirement for 51chromium or 111indium-labelled cells, and allows a wide variety of cell types including neutrophils, monocytes, eosinophils, lymphocytes and melanoma cells to be studied. Optimal concentrations of cells, fetal calf serum, of incubation and washing media, methods of removal of unattached cells and morphological assessment of the human umbilical vein endothelial cells are detailed. We report here the methodology of this new adherence assay with special reference to neutrophils using a range of stimulators that may regulate their attachment to endothelium.

Cell Adhesion↗
PubMed1998

Cytokeratin and neurofilament protein staining in Merkel cell carcinoma of the small cell type and small cell carcinoma of the lung.

Merkel cell carcinoma (MCC) has a small cell variant, indistinguishable in hematoxylin-eosin sections from metastatic small cell carcinoma of the lung (SCCL). To investigate whether intermediate filament expression is helpful in this distinction, 17 MCCs of the small cell type were examined for cytokeratin, as well as neurofilament protein immunostaining, and compared with 59 intermediate-type MCCs and 22 SCCL. With a pan-cytokeratin cocktail (cytokeratin 1-8, 10, 13-16, 19), most (39 of 55) intermediate-type tumors and, more important, 11 of 16 cases of the small cell variant exhibited focal paranuclear staining with dot-like positivity, crescentic positivity, or both. A combined focal (dot-like/crescentic) and diffuse cytoplasmic pan-cytokeratin staining was seen in additional 8 of 55 intermediate and 4 of 16 small cell MCCs. Cytokeratin 20 also evoked focal cytoplasmic staining and occasionally focal and diffuse positivity in the MCCs, irrespective of the subtype. Exclusively diffuse cytokeratin 20 patterns did not occur. Conversely, most SCCL showed a diffuse expression of pancytokeratin, and all cases remained cytokeratin 20 negative. When neurofilament protein was applied, approximately half of the MCCs (25 of 40), including 7 of 11 of the small cell variant, were positive, whereas all SCCL were negative. In conclusion, the cytokeratin and neurofilament protein patterns of small cell MCCs are identical to the pattern of intermediate MCCs but differ from the profile of SCCL, which may help in the differential diagnosis.

Adult↗
PubMed1987

Cell types and cell-substrate interactions in serum-free dissociated cultures of rat hypothalamus.

We have developed a system for the long-term cultivation of hypothalamic neurons at low density in defined serum-free medium, and have identified the major classes of cells in these cultures. Cells prepared from the dissociation of embryonic rat hypothalami are plated, in serum-free medium, onto monolayers of cortical astrocytes. Neurons adhere and begin to extend neurites soon after plating, and survive for up to several weeks in culture. Cell-type-specific immunological markers were utilized to identify neurons and the major classes of glial cells in these cultures. The culture of hypothalamic neurons in serum-free conditions provides a valuable system for the study of the cellular basis of hypothalamic neuronal heterogeneity and functional diversity.

Animals↗
PubMed2002

Doxorubicin-induced death in neuroblastoma does not involve death receptors in S-type cells and is caspase-independent in N-type cells.

Death induced by doxorubicin (dox) in neuroblastoma (NB) cells was originally thought to occur via the Fas pathway, however since studies suggest that caspase-8 expression is silenced in most high stage NB tumors, it is more probable that dox-induced death occurs via a different mechanism. Caspase-8 silenced N-type invasive NB cell lines LAN-1 and IMR-32 were investigated for their sensitivity to dox, and compared to S-type noninvasive SH-EP NB cells expressing caspase-8. All cell lines had similar sensitivities to dox, independently of caspase-8 expression. Dox induced caspase-3, -7, -8 and -9 and Bid cleavage in S-type cells and death was blocked by caspase inhibitors but not by oxygen radical scavenger BHA. In contrast, dox-induced death in N-type cells was caspase-independent and was inhibited by BHA. Dox induced a drop in mitochondrial membrane permeability in all cell lines. Dox-induced death in S-type cells gave rise to apoptotic nuclei, whereas in N-type cells nuclei were non-apoptotic in morphology. Transfection of SH-EP cells with a dominant negative FADD mutant inhibited TRAIL-induced death, but had no effect on dox-induced apoptosis. These results suggest that S-type cells undergo apoptosis after dox treatment independently of death receptors, whereas N-type cells are killed by a caspase-independent mechanism.

Adaptor Proteins, Signal Transducing↗
PubMed2000

GDNF and RET-gene expression in anterior pituitary-cell types.

Glial cell line-derived neurotrophic factor (GDNF) is expressed in many neuronal and non-neuronal tissues during development as well as in adult animals. GDNF signaling is mediated through a two-component system consisting of the so called GDNF receptor-alfa (GFRalpha1) which binds to GDNF. Thereafter this complex binds to and activates the tyrosine kinase receptor RET. In this work, for the first time, we have characterized the expression of both GDNF and RET in the anterior pituitary. First of all, RT-PCR analysis, Western blot and immunohistochemistry of the whole anterior pituitary showed that GDNF, GFRalpha1 and RET are expressed in this gland. Following double-immunofluorescence of consecutive sections we found GDNF immunoreactivity in most cell types, and it was most abundant in corticotrophs (55%), LH (59%) and FSH-producing cells (81%). In contrast, while the majority of somatotrophs (87%) were stained for RET, no positive immunostaining could be detected in other cell types. Taken together, this data indicate that gonadotrophs and corticotrophs are the main source of GDNF synthesized in the anterior pituitary and that the somatotrophs appears to be their target cell. This study provides direct morphological evidences that GDNF may well be acting in a paracrine-like fashion in the regulation of somatotroph cell growth and/or cell function.

Animals↗
PubMed2003

Oxygen sensing in neuroendocrine cells and other cell types: pheochromocytoma (PC12) cells as an experimental model.

A steady supply of oxygen is an absolute requirement for mammalian cells to maintain normal cellular functions. To answer the challenge that oxygen deprivation represents, mammals have evolved specialized cell types that can sense changes in oxygen tension and alter gene expression to enhance oxygen delivery to hypoxic areas. These oxygensensing cells are rare and difficult to study in vivo. As a result, pheochromocytoma (PC12) cells have become a vital in vitro model system for deciphering the molecular events that confer the hypoxia-resistant and oxygen-sensing phenotypes. Research over the last few years has revealed that the hypoxia response in PC12 cells involves the interactions of several signal transduction pathways (Ca2+/calmodulin-dependent kinases, Akt, SAPKs, and MAPKs) and transcription factors (HIFs, CREB, and c-fos/junB). This review summarizes the current understanding of the role these signal transduction pathways and transcription factors play in determining the hypoxic response.

Animals↗
PubMed1990

1990 cell typings in the International Cell Exchange.

1. A yearly summary of the previous year's cells typed through the International Cell Exchange allows a participating laboratory to compare its own performance with 292 currently participating exchange laboratories, inasmuch as each laboratory receives its individual antigen report. We present an annual summary for the 1990 typings of 40 cells sent for Class I and 20 cells sent for Class II antigens. 2. The mean detection percentages and the detection ranges for 21 WHO-designated (well-defined) and 21 WHO-provisional (with "w" designations, less well-defined) antigens were determined for the Class I cells typed in 1990. Seventeen WHO antigens showed 95% or greater detection levels. The remaining WHO antigens showed at least 90% agreement, with the exception of B38. More variation in detection is observed in the WHO-provisional antigens. Aw33, Bw50, Bw60, and Bw62 showed 90% or greater average detection percents. In recent years, antigens such as Bw46 and Bw70, have shown great improvement in detection. 3. The percent discrepancy rates of 8 HLA-A,B antigens typed 4 times or more in 1990 were presented as well as the total percent discrepancy rates for all Class I antigens. Comparison of 1990 figures with those of 1988 and 1989 shows a marked decrease in the total discrepancy rates. 4. The number of false negatives and false positives for the Class I antigens indicates that few laboratories have trouble typing the WHO antigens; as many as 115 laboratories had 0 misses. However, a greater number of laboratories missed the less well-defined WHO-provisional antigens: 7 laboratories had 0 misses for all the antigens and 4 laboratories had perfect records (0 false negatives and false positives) for cells typed in 1990. 5. In 1990, the cell exchange continued to study new cell variants. An A10 (A26x34) variant was detected in 4 cells and another possible variant, B7x40 (DT), was determined in 3 cells. 6. The average detection percentages and detection ranges were determined for 23 Class II antigens. Improved detection is indicated. At least 9 Class II antigens showed 90% or greater agreement level, of which at least 4 had 95% or greater mean detection. 7. Since the incorporation of DNA typing results in the B-cell line exchange reports in July 1990, the Class II antigen splits in 11 cells have been confirmed or clarified. Two Class II variants were also confirmed by the DNA laboratories. Presently, 145 serology and 7 DNA laboratories are in this exchange.(ABSTRACT TRUNCATED AT 400 WORDS)

DNA↗
PubMed1995

Support versus inhibition of hematopoiesis by two characterized stromal cell types.

Stromal cells are believed to regulate hematopoiesis through direct cell-cell contact interactions and the release of growth factors. Many questions remain, however, about their lineage derivation and functional heterogeneity. We have previously shown that the adherent nontransformed, nonimmortalized murine bone marrow stromal cell population consists of three cell types which could be grown separately in vitro. Based on the phenotype characterization and expression of surface antigens, we proposed a classification listing for murine bone marrow stromal cells as macrophages, endothelial-like cells and myofibroblasts that display smooth muscle-like characteristics in culture. The present study describes the ability of each of these freshly isolated separated murine stromal cell populations to support the growth of primitive hematopoietic stem cells previously characterized as highly enriched in long-term repopulating cells (LTRC). Of the three stromal cell types tested only the myofibroblasts were capable of support for multilineage hematopoiesis derived in vitro from LTRC in a cloning ring culture system. Endothelial-like cells had an inhibitory effect on the proliferation of LTRC and their descendant cells that was induced by exogenous growth factors. This inhibitory activity was present in a low molecular weight filtrate of endothelial-like cells culture medium. This suggests an essential role for marrow stroma myofibroblasts in the support of proliferation of hematopoietic cells at the stage of early divisions of primitive hematopoietic stem cells and endothelial-like cells as negative regulators of this proliferation.

Alkaline Phosphatase↗
PubMed1979

Role of aggregation factor and cell type in sponge cell adhesion.

A pair of sponge species, Microciona prolifera and Halichondria bowerbanki, which lack mutual species specificity in their aggregation "factor", are useful in establishing the mechanisms of action of these factors. These sponges were dissociated both mechanically, which leaves the factor on the cell surface, and by Humphrey's (1963) method, which isolates the factor from the cells. The adhesive specificities which arose, in the various combinations tested, point to an intercellular factor bridge consisting of a single symmetrical unit. An analysis of most other workers' results is consistent with this interpretation. However, MacLennan and Dodd's (1967) results using other species would require a bridge consisting of two or more asymmetrical units. Differences were found in the specificity of adhesion of various types of cells within a single species. This presents a heretofore unconsidered problem in assesing the adhesive factor's mechanism of action. Three structurally distinct cell types were separated from a suspension of dissociated Microciona cells by velocity sedimentation. These cells differ greatly in adhesiveness. The differences in adhesion are correlated with numbers and positions of cells incorporated into aggregates. Such differences are considered in explaining the mechanism of action of the factors.

Animals↗
PubMed1978

Differential expression of the gene for the large subunit of ribulose bisphosphate carboxylase in maize leaf cell types.

Mesophyll cells and bundle sheath cells, the dimorphic photosynthetic cell types in the C4 plant Zea mays, differ in protein composition. In particular, the large subunit of the chloroplast enzyme ribulose-1,5-bisphosphate carbocylase (EC 4.1.1.39) is found entirely or almost exclusively in bundle sheath cells. The DNA sequence coding for this polypeptide is contained in the chloroplast DNA of both mesophyll cells and bundle sheath cells. RNA complementary to this coding sequence has been detected in RNA from bundle sheath cells, but is almost or entirely absent from mesophyll cells. Similarly, translatable mRNA for this polypeptide has been detected in RNA from bundle sheath cells, but not from mesophyll cells. Portions of the 4200 base pair maize plastid DNA sequence Bam 9 outside the large subunit gene region appear to be transcribed in mesophyll cells. Thus differential gene expression at the mRNA level has been directly demonstrated to occur in these two cell types.

Carboxy-Lyases↗
PubMed1975

Differentiation in vitro of larval cell types from early embryonic cells of Drosophila melanogaster.

A variety of cell types develop when cells of 6 1/2-8 1/2 h Drosophila embryos are cultured in an improved medium. Nerve, muscles, fat-body, chitin-secreting, and macrophage-like cells (possibly haemocytes) appear in the first 24 h and mature over the next week. Tracheal, imaginal disc, a second stage of the macrophage-like, and a anumber of unidentified fibroblastic and epithelial cells appear in the 2nd and 3rd week, following a resumption of cell multiplication. There is some organization of some of the cell types into higher structures.

Adipose Tissue↗
PubMed1995

Standard and variant CD44 isoforms are commonly expressed in lung cancer of the non-small cell type but not of the small cell type.

Cluster of differentiation 44 (CD44) encompasses a polymorphic family of cell membrane glycoproteins involved in the mechanism of tumour invasion and metastasis. Since non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) display very different rates of progression, a significant discrepancy in their CD44 expression profiles is to be expected. An immunohistochemical study was undertaken on the expression of standard CD44 (CD44s) and the variant isoforms containing the domains encoded by variant exon 3 (CD44v3) or variant exon 6 (CD44v6) in paraffin-embedded bronchial biopsy specimens from 32 NSCLC cases and 11 SCLC cases. An absolute lack of immunoreactivity for CD44s, CD44v3, and CD44v6 was obtained in every case of SCLC, whereas 28 of the 32 NSCLC cases showed a positive immunoreaction for at least one of the three epitopes investigated. In conclusion, the occurrence of standard and variant CD44 isoforms in NSCLC and their absence in SCLC suggest the possibility that CD44 is in some way instrumental in conditioning the biological behaviour of NSCLC, but not of SCLC, whose metastatic cascade would be set in motion by the activation of hitherto unidentified, CD44-independent pathways.

Adult↗
PubMed2026

Integrative evidence-knowledge marker selection enhances LLM-based cell type annotation in single-cell RNA-seq analysis.

BACKGROUND: Cell type annotation is essential for gaining biological insight from single-cell RNA sequencing data, yet manual labeling remains time-consuming and difficult to reproduce. Various computational approaches have been developed to automate this process, and recent studies suggest that large language models can infer cell types with promising accuracy in single-cell analysis. However, most workflows still rely on cluster-specific markers derived from gene expression alone or manual curation. As a result, marker selection can be sensitive to statistical criteria and dataset-dependent bias, which may lead to the selection of less informative genes or missing important markers, while providing limited biological context. RESULTS: To address this limitation, we introduce CELLIA, an LLM-based workflow for automated and robust cell type annotation. CELLIA employs an integrative evidence-knowledge marker selection strategy that combines statistical differential expression criteria with curated tissue-specific marker resources to identify informative marker genes. In benchmarking analyses of 102 cell types, this approach improved agreement with manual annotations. In addition, CELLIA achieved higher agreement in subtype-level analyses of closely related immune populations and was further evaluated in a non-immune stromal subtype setting, covering 25 cell types in total. CONCLUSION: By integrating evidence-knowledge from gene expression with curated biological prior knowledge, CELLIA provides a more stable marker selection and improves the reliability of LLM-cell type annotation.

Cell type annotation↗