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Results for “Cell Lineage”

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At least 361 records · Page 20Linked to original sources

PubMed2001

Role for transcription Pax5A factor in maintaining commitment to the B cell lineage by selective inhibition of granulocyte-macrophage colony-stimulating factor receptor expression.

During early B lymphopoiesis, developing B cells maintain lineage commitment despite the local presence of myeloid lineage-promoting cytokines such as GM-CSF and IL-3. Previous observations suggest that the B cell-specific transcription factor Pax5A (paired box 5A transcription factor) plays a role in maintaining B cell lineage commitment by limiting expansion and survival of early IL-3/GM-CSF-dependent myeloid lineage cells. To define a mechanism by which Pax5A can exert these inhibitory effects on myeloid lineage differentiation, an inducible form of the Pax5A protein was expressed in the myeloid cell line FDC-P1. This cell line models myeloid progenitors in that it responds to the survival and growth-potentiating effects of IL-3 and GM-CSF. We observed that enforced expression of Pax5A selectively suppressed proliferation in response to GM-CSF, but not IL-3. This effect was associated with specific down-regulation of GM-CSFR alpha-chain, but not beta-chain expression. These data provide a molecular mechanism to enforce commitment to the B cell lineage despite the presence of GM-CSF, a factor that has been shown to convert early developing B cells to the myeloid lineage. Furthermore, they indicate a role for B cell Pax5A expression in maintaining rather than directing commitment to the B cell lineage.

Animals↗

PubMed1986

Cells containing IgE in the intestinal mucosa of mice infected with the nematode parasite Trichinella spiralis are predominantly of a mast cell lineage.

To determine whether IgE+ cells in the intestinal mucosa of nematode-infected mice were of a mast cell or a lymphocyte lineage, the intestinal mucosae of mast cell-deficient w/wv mice were examined for IgE+ cells after inoculation with Trichinella spiralis muscle-stage larvae. Immunofluorescence staining techniques were used to detect IgE associated with cells in the intestinal mucosa. Comparisons were made among four strains of mice, w/wv (mast cell-deficient), +/+ (normal congenic littermates of w/wv), BALB/c, and SJL, that were either uninfected controls or inoculated with T. spiralis. Tissue sections from the small intestine of T. spiralis-infected BALB/c, SJL, and +/+ mice were fixed in ethanol and were stained with an affinity-purified F(ab')2 rabbit anti-mouse IgE followed by FITC goat anti-rabbit IgG. Large numbers of cells in the intestinal mucosa exhibited bright fluorescence. When other sections of intestines from these mice were processed in Carnoy's fixative and were stained with alcian blue at low pH (a metachromatic stain for mast cells) or alcian blue followed by immunofluorescence staining for IgE, large numbers of mast cells were observed in the intestinal mucosa, and 70 to 90% stained positively for IgE. There was a considerable number of cells in the intestinal mucosa which were IgE+ but which did not stain with alcian blue. Few alcian blue-positive cells and no IgE+ staining cells were present in the intestinal mucosa of control, uninfected +/+, BALB/c, and SJL mice. To determine whether these IgE+ alcian blue-negative cells were of a lymphocyte or a mast cell lineage, the mast cell-deficient w/wv mouse strain was examined after infection with T. spiralis. In contrast to BALB/c, SJL, or +/+ mice, few cells in the intestinal mucosa of T. spiralis-infected w/wv mice stained with alcian blue or were positive for IgE. However, when the IgE response in the MLN of the w/wv mice was compared to the IgE response of BALB/c, SJL, and +/+ mice, numerous IgE+ cells, but no alcian blue-positive cells, were observed in the parenchyma of the MLN from all four strains of T. spiralis-infected mice. In addition, flow microfluorometric analysis of MLN cells stained for surface IgE in suspension showed a comparable proportion of IgE-bearing cells, which were mostly B lymphocytes, among all four strains of T. spiralis-infected mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1989

Cell lineage markers in premalignant and malignant colonic mucosa.

Normal colonic epithelial cells consist of several cell types or lineages that are thought to arise from a common stem cell precursor. Neoplastic transformation may occur at different stages in the differentiation of a colonic stem cell to produce tumors that may retain characteristic cell lineage phenotypes. In this study, immunohistochemical techniques were used to identify cell lineage-related markers in fetal, normal, hyperplastic, adenomatous, and cancerous colonic tissue. These markers consisted of secretory component (columnar cells), a purified mucin antigen (mucous or goblet cells), chromogranin A (enteroendocrine cells), lysozyme (Paneth cells), and carcinoembryonic antigen (panepithelial cell marker). Colonic neoplasms, like normal mucosa, predominantly expressed the markers of columnar and goblet cell lineages. Chromogranin A was expressed in a small population of cells in most normal and fetal colonic crypts. Chromogranin A reactive cells were found in 55% of hyperplastic polyps, 31% of adenomatous polyps, and 33% of carcinomas. Lysozyme reactivity was rare in fetal, normal, and hyperplastic specimens, but was present in 86% of adenomas and 40% of carcinomas. Of 42 primary carcinomas, 9% were "pluripotent" and expressed markers of all four cell lineages. In addition to columnar and goblet cell markers, 7% expressed both enteroendocrine and Paneth cell markers, 17% expressed enteroendocrine cell markers, and 24% expressed Paneth cell markers. Two cases (5%) lacked expression of any of the cell lineage markers. The remainder expressed only columnar and goblet cell markers. The markers used in this study appear to identify the major cell lineages of fetal and normal colonic epithelium and can be used to delineate the altered cell lineage phenotypes in premalignant and malignant colonic mucosa.

Biomarkers, Tumor↗

PubMed1998

SHP-1 deficiency in B-lineage cells is associated with heightened lyn protein expression and increased lyn kinase activity.

SHP-1 protein tyrosine phosphatase is a critical regulator of signal transduction in hematopoietic cells. In the present study, we derived two pre-B cell lines, PBCL-1 and PBCL-2, from normal and SHP-1-deficient motheaten mice, respectively, and characterized hyperphosphorylated proteins in PBCL-2 cells to identify SHP-1-regulated molecules. Two proteins of 56 and 53 kDa (p56/p53) in PBCL-2 cells showed heightened phosphorylation (3- to 6-fold) in comparison with those in PBCL-1. p56/p53 were identified as the two forms of the lyn protein tyrosine kinase (p56/p53lyn), which showed increased kinase activity in PBCL-2 cells. Interestingly, the protein levels of p56/53lyn were found to be 3- to 6-fold higher in PBCL-2 cells than those in PBCL-1, whereas the transcript levels of lyn in the two cell lines were comparable. A modest increase in p56/53lyn protein expression was also detected in primary spleen B cells of motheaten mice. Thus SHP-1 deficiency in B-lineage cells, especially pre-B cells, is associated with increased lyn protein expression and kinase activity. These data indicate a role for SHP-1 in regulating lyn through a post-transcriptional mechanism.

Animals↗

PubMed2001

Morphological changes and cellular dynamics of oligodendrocyte lineage cells in the developing vertebrate central nervous system.

Oligodendrocyte precursor cells (OPCs) originate in multiple restricted regions of the developing central nervous system (CNS). Here, we focus on morphological changes of oligodendrocyte lineage cells and their cellular dynamics including cell motility and proliferation. Morphological studies with molecular markers for OPCs suggest distinct spatiotemporal patterns of OPC migration in vivo, which are directly demonstrated by application of exogenous fluorescent markers to OPCs. Extensive proliferation of OPCs in the CNS parenchyma is also demonstrated by pulse labeling of the cells with bromodeoxyuridine. The results strongly suggest that oligodendrocyte lineage cells are highly motile and actively proliferate with an elongated morphology. These data provide insights into the potential molecular mechanisms of OPC dispersal throughout the CNS.

Animals↗

PubMed2002

The unexpected landscape of in vivo somatic mutation in a human epithelial cell lineage.

Few data exist on somatic mutation in the epithelial cell lineages that play a central role in human biology and disease. To delineate the "landscape" of somatic mutation in a human epithelial cell lineage, we determined the frequency and molecular nature of somatic mutations occurring in vivo in the X-linked HPRT gene of kidney tubular epithelial cells. Kidney epithelial mutants were frequent (range 0.5 to 4.2 x 10(-4)) and contained a high proportion of unreported HPRT base substitutions, -1-bp deletions and multiple mutations. This spectrum of somatic mutation differed from HPRT mutations identified in human peripheral blood T lymphocytes and from germ-line HPRT mutations identified in Lesch-Nyhan syndrome or hyperuricemia patients. Our results indicate that DNA damage and mutagenesis may have unusual or mechanistically interesting features in kidney tubular epithelium, and that somatic mutation may play a more important role in human kidney disease than has been previously appreciated.

Cells, Cultured↗

PubMed1998

Ablation of Nrf2 function does not increase the erythroid or megakaryocytic cell lineage dysfunction caused by p45 NF-E2 gene disruption.

Maf recognition elements (MAREs or NF-E2 binding sites) have been shown to be vital for erythroid- and megakaryocyte-specific gene expression. Transcription factor NF-E2 is composed of p45, a large subunit belonging to the CNC family proteins, and a small Maf subunit, and is thought to activate transcription through its binding to MAREs in both the erythroid and megakaryocytic cell lineages. While p45 gene knockout mice exhibit thrombocytopenia due to abnormal terminal differentiation of megakaryocytes, and the mutant mice die of massive bleeding within a week after birth, anemia is not apparent in these animals. Disruption of the nrf2 gene, encoding another CNC family protein, results in no hematological abnormalities. We have therefore tested the hypothesis that Nrf2 might compensate for the p45 deficiency in erythroid lineage cells of p45-knockout mice, thereby masking the anticipated anemia. However, we failed to detect any greater failure in either erythroid or megakaryocytic cell development in Nrf2 plus p45 compound mutant mice as compared to with either individual homozygous mutation. These data suggest that p45 and Nrf2 may both be dispensable for hematopoietic cell development, and that other factors regulate erythroid- and megakaryocyte-specific gene expression through their required MAREs.

Anemia↗

PubMed2025

CLADES: A Programmable Cascade of Genes for Cell Lineage Analysis and Manipulation.

In the Drosophila brain, neuronal diversity originates from approximately 100 neural stem cells, each dividing asymmetrically. Precise mapping of cell lineages at the single-cell resolution is crucial for understanding the mechanisms that direct neuronal specification. However, existing methods for high-resolution lineage tracing are notably time-consuming and labor-intensive. Here, we outline the best practices for lineage tracing using CLADES (cell lineage access driven by an edition sequence), a revolutionary approach to neuronal lineage tracing that addresses the limitations of previous methods. CLADES effectively traces the birth order of neurons using approximately 100 samples. The technique relies on a genetic cascade of reporter activations and deactivations that delineate lineage progression through color-coded markers. This system not only facilitates the detailed mapping of neuronal lineages but also holds the potential to be applied to tracking biological events and producing cell types for therapeutic purposes.

Animals↗

PubMed1998

Fate map and cell lineage relationships of thoracic and abdominal mesodermal anlagen in Drosophila melanogaster.

We have examined the cell lineage of larval and imaginal precursors of the mesodermal anlage between 10% and 60% egg length (EL) by homotopic single-cell transplantations at the blastoderm stage. Clones in the larval somatic muscles and in the fat body were derived from transplantations everywhere between 10% and 60% EL along the ventral side of the embryo. Clones frequently overlap these tissues and can extend over a maximum of four segments in the larval somatic muscles or over two morphologically-distinct parts in the fat body. Clones in the gonadal mesoderm overlap with other mesodermal derivatives and exhibit different mitotic behaviour in the two sexes. We present a blastoderm fate map for the fat body, the larval somatic muscles and the gonadal mesoderm. Clones in the imaginal muscle precursors of the abdomen, as well as of the thorax, always show a common cell lineage with larval somatic muscles and partly with other mesodermal tissues. These clones of imaginal derivatives are always found within a single segment, while the overlapping clone parts in the larval somatic muscles can label up to three segments.

Abdomen↗

PubMed1999

Towards Automatic Construction of Cell-Lineage of C. elegans from Nomarski DIC Microscope Images.

This study aims at automatic construction of a cell lineage from 4D (multi-focal, time-lapse) images, which are taken using a Nomarski DIC (differential-interference contrast) microscope. A system with such abilities would be a powerful tool for studying embryo genesis and gene function based on mutants, whose cell lineage may differ from that of wild types. We have designed and implemented a system for this purpose, and examined its ability through computational experiments. The procedure of our system consists of two parts: (1) Image processing which detect the positions of the nuclei from each 2D microscope image, and (2) Constructing a hypothetical cell lineage based on the information obtained in (1). We have also developed a tool which allows a human expert to easily filter out erroneous nuclei candidates generated in (1). We present computational results and also discuss other ideas which may improve the performance of our system.

Journal Article↗

PubMed1993

Making sense of cell lineage.

In this article I describe what I see as the sources of confusion in the description and interpretation of cell lineage data. I concentrate on lineage in the nervous system, since that is my interest, but most of the arguments are broadly applicable. Since there are these differences between workers in the field, all will not agree with my perspective, but perhaps a consensus can evolve from the discussion. I see the problem as having two facets: First, there is a confusion surrounding terminology, which leads to too many different types of studies to be considered as studies of cell lineage; and second, there is some confusion about what can validly be concluded from a study of cell lineage.

Animals↗

PubMed1990

Hypertrophic chondrocytes. The terminal stage of differentiation in the chondrogenic cell lineage?

Chondrocytes emerging in the limb or other locations during embryogenesis are currently considered terminally differentiated cells and thus represent the last stage of differentiation in the chondrogenic cell lineage. Most chondrocytes, however, undergo further major phenotypic changes during late embryogenesis and early postnatal life as they take part in the endochondral ossification process. During this process, "resting" chondrocytes first enter an active, proliferative phase and then develop into large, round hypertrophic chondrocytes with unique phenotypic traits. The question thus arises as to whether hypertrophic chondrocytes actually represent the terminal stage of differentiation in the chondrogenic lineage. To assess the developmental position of these cells along the lineage, we examined the expression of four genes encoding extracellular matrix components in chondrocytes undergoing endochondral ossification in chicken tibial growth cartilage. We found that the steady-state levels of mRNAs coding for proteoglycan core protein increased in regions of cartilage destined for endochondral ossification. Similarly, type II collagen gene expression increased markedly in proliferating chondrocytes and then returned to basal levels in hypertrophic chondrocytes. As revealed by in situ hybridization, type X collagen gene expression was undetectable in resting and early proliferating chondrocytes and was detectable in hypertrophic chondrocytes. Osteonectin synthesis appeared to characterize chondrocytes in the resting, proliferating, and hypertrophic zones of growth cartilage. The protein was scarce, however, and cell-associated in the former zones, although it was very abundant and matrix-associated in the hypertrophic zone. Clearly, the emergence of hypertrophic chondrocytes during endochondral ossification is accompanied by marked quantitative and qualitative changes in gene expression. Interestingly, these changes occur during or immediately after the period of active chondrocyte proliferation. On the premises of the cell lineage definition proposed by Holtzer, the above data suggest that the hypertrophic chondrocytes represent the terminal stage of differentiation in the chondrogenic cell lineage.

Animals↗

PubMed1999

Precise developmental regulation of Ets family transcription factors during specification and commitment to the T cell lineage.

Ets family transcription factors control the expression of a large number of genes in hematopoietic cells. Here we show strikingly precise differential expression of a subset of these genes marking critical, early stages of mouse lymphocyte cell-type specification. Initially, the Ets family member factor Erg was identified during an arrayed cDNA library screen for genes encoding transcription factors expressed specifically during T cell lineage commitment. Multiparameter fluorescence-activated cell sorting for over a dozen cell surface markers was used to isolate 18 distinct primary-cell populations representing discrete T cell and B cell developmental stages, pluripotent lymphoid precursors, immature NK-like cells and myeloid hematopoietic cells. These populations were monitored for mRNA expression of the Erg, Ets-1, Ets-2, Fli-1, Tel, Elf-1, GABPalpha, PU.1 and Spi-B genes. The earliest stages in T cell differentiation show particularly dynamic Ets family gene regulation, with sharp transitions in expression correlating with specification and commitment events. Ets, Spi-B and PU.1 are expressed in these stages but not by later T-lineage cells. Erg is induced during T-lineage specification and then silenced permanently, after commitment, at the beta-selection checkpoint. Spi-B is transiently upregulated during commitment and then silenced at the same stage as Erg. T-lineage commitment itself is marked by repression of PU.1, a factor that regulates B-cell and myeloid genes. These results show that the set of Ets factors mobilized during T-lineage specification and commitment is different from the set that maintains T cell gene expression during thymocyte repertoire selection and in all classes of mature T cells.

Animals↗

PubMed2004

Expression of Notch signalling markers in bone marrow cells that differentiate into a liver cell lineage in a rat transplant model.

Notch signalling pathway plays an important role in cell differentiation. To investigate the implications of Notch signalling in the differentiation of rat bone marrow (BM) cells into a liver cell lineage, we used cultured BM cells to examine the mRNA expression of Musashi-1, which positively regulates Notch signalling, and made a transplant model to examine the protein expression of Notch signalling markers. For the in vivo experiment, BM cells were collected from transgenic rats expressing green fluorescence protein (GFP) and transplanted into the spleens of recipient rats, in which liver damage had been induced with carbon tetrachloride. The expression of Notch receptor 1 (Notch-1), Jagged-1 and Musashi-1, in the transplanted GFP-positive BM cells was investigated by immunohistochemistry. The expression of the liver-specific proteins, alpha-fetoprotein and cytokeratin19 was also investigated. Musashi-1 mRNA became detectable in the BM cells on culture day 7 in vitro. After transplantation, GFP-positive BM cells were observed in the portal areas of the recipient's livers. Notch-1, Jagged-1, Musashi-1, alpha-fetoprotein and cytokeratin19 were all expressed in the transplanted BM cells. These results suggest that the Notch signalling pathway plays a role in the differentiation of BM cells into a liver cell lineage.

Journal Article↗

PubMed1999

Maturation decreases responsiveness of human bone marrow B lineage cells to stromal-derived factor 1 (SDF-1).

We compared the chemotactic responsiveness of different subsets of human B lineage cells to stromal derived factor-1 (SDF-1). High percentages (30-40% of input) of purified bone marrow progenitors including non-B lineage progenitors, pro-B cells, and pre-B cells migrated to SDF-1alpha, demonstrating that SDF-1 is an efficacious chemoattractant of these cells. Pro-B cells responded optimally to a lower concentration of SDF-1 than other subsets, demonstrating that SDF-1 is a more potent chemoattractant of this subset. A lower percentage (10-15% of input) of mature B lymphocytes migrated to SDF-1alpha than pro-B cells, demonstrating that responsiveness of B lineage cells to SDF-1 decreases during differentiation. Inhibition by anti-CXCR4 mAb demonstrated that migration of B lineage cells to SDF-1 was completely dependent on CXC chemokine receptor-4 (CXCR4). Mature B cells expressed higher levels of CXCR4 receptors than uncommitted progenitors and pro-B cells, despite differences in responsiveness to SDF-1. CXCR4 receptors expressed by unresponsive and SDF-1-responsive B cells bound SDF-1alpha with similar affinities (K(D) = 1.7-3.3 x 10(-9) M). Therefore, elements downstream from CXCR4 appear to regulate responsiveness of B cells to SDF-1. We speculate that SDF-1 and CXCR4 direct migration of progenitor cells in microenvironments that promote B lymphopoiesis.

B-Lymphocytes↗

PubMed1998

Visualization of mitotic radial glial lineage cells in the developing rat brain by Cdc2 kinase-phosphorylated vimentin.

Although accumulating data reveal patterns of proliferation, migration, and differentiation of neuronal lineage cells in the developing brain, gliogenesis in the brain has not been well elucidated. In the rat brain, vimentin is selectively expressed in radial glia and in their progeny, not in oligodendrocytes or neurons from embryonic day 15 (E15) until postnatal day 15 (P15). Here we examined mitotic radial glial lineage cells in the rat brain E17-P7, using the monoclonal antibody 4A4, which recognizes vimentin phosphorylated by a mitosis-specific kinase, cdc2 kinase. In the neocortex, mainly radial glia in the ventricular zone, but not their progeny, underwent cell division. In contrast, not only radial glia but also various types of radial glial progeny including Bergmann glia continued to proliferate in the cerebellum. Radial glia in the neocortex divided horizontally, obliquely, and vertically against the ventricular surface. The percentage of the vertical division increased with progress in the stage of development, concurrently with the decrease of the population of horizontal divisions. Thus, the monoclonal antibody 4A4 provides an useful tool to label mitotic glia in the developing brain and revealed different patterns of gliogenesis in the neocortex and cerebellum. A possibility is discussed that the dynamics of mitotic orientation observed here may be related to the change of the pattern of gliogenesis during development.

Animals↗

PubMed2001

Connective tissue changes in ileal Crohn's disease: relationship to disease phenotype and ulcer-associated cell lineage.

PURPOSE: Abnormalities of enteric collagen and smooth-muscle cell content have been documented in Crohn's disease. We studied the relationships among connective tissue changes, disease "type," and other disease features using immunohistochemistry and image analysis. METHODS: Twenty consecutive ileal resections for Crohn's disease and ten normal terminal ileal specimens were evaluated using conventional histopathologic examination. Monoclonal antibodies to smooth-muscle actin and Type III collagen fibers were used to determine the percentage area of the submucosa occupied by these constituents using image analysis. RESULTS: There were no significant differences in smooth-muscle content among stenosed, perforated, and ulcerated specimens. There was a significantly increased submucosal Type III collagen content in stenosed vs. other types. The only factor that correlated with smooth-muscle cell content was the amount of ulcer-associated cell lineage present. CONCLUSIONS: Increased deposition of Type III collagen fibers rather than smooth-muscle proliferation is associated with a stenotic phenotype. Loss of Type III collagen fibers may play a role in the development of perforating complications. We have found no evidence that smooth-muscle cells are the source of Type III collagen fiber production although there is evidence that ulcer-associated cell lineage may be related to the stimulus leading to submucosal neomuscularization.

Cell Division↗

PubMed1997

TEL/AML1 fusion gene resulting from a cryptic t(12;21) is uncommon in adult patients with B-cell lineage ALL and CML lymphoblastic transformation.

TEL is a new member of the ETS-like family on chromosome 12 and forms fusion genes with several partners in leukemia. Among these fusion genes, the TEL/AML1 translocation resulting from t(12;21) is found in approximately one quarter of the childhood B-cell lineage acute lymphoblastic leukemia (ALL) cases and its prognosis is excellent. We examined 42 adult patients with B-cell lineage ALL and 13 adult patients with lymphoblastic transformation of chronic myeloid leukemia (CML) to detect TEL/AML1 fusion genes using the reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blotting, but no translocation was detected. These findings indicate that absence of the TEL/AML1 fusion transcript partly correlates with the poorer outcome of adult B-cell lineage ALL as compared with childhood ALL and the TEL/AML1 fusion transcript is specific for pediatric B-cell lineage ALL.

Adolescent↗