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At least 451 records · Page 25Linked to original sources

PubMed2005

Expression of retinoid receptors in multiple cell lineages in the gastric mucosae of mice and humans.

BACKGROUND AND AIM: In mice and humans, the gastric epithelial progenitors undergo proliferation and bipolar migration from the isthmus associated with their differentiation into mucus-, acid- and pepsinogen-secreting cell lineages. Little is known about factors that control the dynamics of these isthmal progenitor cells. Retinoids have long been known as chemopreventive agents against gastric mucosal damage and carcinogenesis. The aim of the present study was to examine the cellular localization of the various retinoid receptors proteins (RAR and RXR) in the gastric epithelium of mice and humans. METHODS: Gastric antral biopsies of normal individuals and the oxyntic and antral regions of the mouse stomach were processed for immunohistochemistry using anti-RAR and anti-RXR antibodies. To label the progenitor cell zone, some sections were also probed with antibodies specific for proliferating cell nuclear antigen. RESULTS: The immunoprobed oxyntic mucosal sections of the mice showed that RXRbeta protein was present in the epithelial isthmal cells, neck cells, zymogenic cells and some pit and parietal cells. In addition, RARbeta was found in isthmal and neck cells, and RARgamma was mainly found in neck cells. In the mouse antrum, only RXRbeta was detected in the isthmal cells and their pit and gland cell descendents. In humans, immunoprobed antral sections showed that RARbeta, RARgamma, RXRalpha and RXRgamma proteins are expressed in the isthmal, pit and gland cells. CONCLUSIONS: Retinoid receptors are expressed in multiple cell lineages of the mouse and human gastric epithelium and may, therefore, account for the possible effects of retinoids on gastric epithelial cell proliferation and differentiation.

Adult↗

PubMed1990

A new technique using an aggregating antibody against glycophorin-A for purging Ficoll-Paque-separated leucocytes of contaminating erythroid lineage cells.

Ficoll-separated leucocytes used for phenotyping may be contaminated with erythroblasts or erythrocytes, which can cause problems in cytofluorography, especially if erythroid lineage cells outnumber leucocytes in the preparation. Different means have been described for removing erythroid cells from leucocyte preparations, such as BD-FACS lysing solution, hypotonic shock and ammonium chloride, but none of these is entirely satisfactory. In my hands all these techniques damaged the leucocytes to a greater or lesser extent and did not adequately eliminate the erythroblasts, sometimes not even the reticulocytes and erythrocytes. To obtain pure leucocyte suspensions, I developed a new technique based on an aggregating antibody (alpha-Gly-A, 733/8F7, from BioCarb, Sweden) directed against glycophorin-A which is found on the cell surface of erythroid lineage cells. Agglutinated erythroid cells could be removed by filtration or low-speed centrifugation. With the new technique there was no loss or damage of the leucocytes.

Adult↗

PubMed2000

New approach to cell lineage analysis in mammals using the Cre-loxP system.

The Cre-loxP site-specific recombination system was used for cell lineage analysis in mammals. We constructed an expression plasmid, pCETZ-17, which consists of cytomegalovirus enhancer/chicken beta-actin promoter (CAG), a portion of the rabbit beta-globin gene, loxP-flanked DNA sequence (containing enhanced green fluorescent protein (EGFP) cDNA), and lacZ gene encoding E. coli beta-galactosidase (beta-gal). When circular pCETZ-17 plasmid DNA was microinjected into the pronuclei of fertilized eggs and these eggs were allowed to develop to two-cell stage, 62.8% (59/94) of the two-cell embryos exhibited distinct fluorescence in one or both blastomeres, but never expressed lacZ protein, as evaluated by histochemical staining with X-Gal, a substrate for beta-gal. When both circular plasmids, pCETZ-17 and pCAG/NCre (containing CAG and DNA sequences encoding nuclear location signal and Cre), were co-injected into fertilized eggs, almost all (87.0%, 47/54) embryos exhibited low or no fluorescence, but 51.9% (27/52) exhibited positive staining for beta-gal activity. This indicates that transient expression of the Cre recombinase gene removed the loxP-flanked DNA sequence in pCETZ-17 and then caused expression of the downstream lacZ sequence. We next microinjected pCETZ-17 into the pronuclei of fertilized eggs, cultured these injected eggs for 1 day, and collected only two-cell embryos expressing EGFP in both blastomeres. One blastomere of the EGFP-expressing two-cell embryos was microinjected with pCAG/NCre, and these treated embryos were cultured for 1 day up to four-cell stage. When the developing four-cell embryos were subjected to staining with X-Gal, cell lineage-related staining pattern for beta-gal activity was observed in most (77.8%, 7/9) embryos. These findings were further confirmed using two-cell embryos derived from a transgenic mouse line carrying CETZ-17 transgene. Thus, our system, which is based on transient expression of the Cre recombinase gene directly introduced into nuclei of embryonic cells by microinjection, is a powerful means for cell lineage analysis in mammals.

Animals↗

PubMed2006

Differentiation of human ameloblast-lineage cells in vitro.

Previous studies have shown that ameloblast-like cells can be selectively cultured from the enamel organ in a serum-free medium with low calcium concentrations. The purpose of this study was to further characterize this culture system to identify differentiated ameloblast-lineage cells. Tooth organs from 19-24-wk-old fetal cadavers were either frozen and cryosectioned for immunostaining, or digested in collagenase/dispase for cell culture. The cells were grown in keratinocyte media supplemented with 0.05 mM calcium, and characterized by morphology and immunofluorescence. Epithelial clones with two distinct morphologies, including smaller cobblestone-shaped cells and larger (5-15 times in size) rounded cells, began to form between day 8 and day 12 after culture. The cobblestone-shaped cells continued to proliferate in culture, while the larger cells proliferated slowly or not at all. These larger cells formed filopodia, usually had two or more nuclei and a radiating cytoplasm at the cell margin, and were more abundant with increasing time in culture. Both cell types stained for cytokeratin 14, and the larger cells appeared more differentiated, showing stronger staining for amelogenin and ameloblastin. Immunofluorescence of the tooth bud sections showed staining for these matrix proteins as ameloblasts differentiated from the inner enamel epithelium. These results show the successful culture of differentiating ameloblast-lineage cells, and lay a foundation for use of these cells to further understand ameloblast biology with application to tooth enamel tissue engineering.

Ameloblasts↗

PubMed1999

Molecular cloning and genomic organization of mouse homologue of Drosophila germ cell-less and its expression in germ lineage cells.

Primordial germ cells (PGCs) are founder cells of all gametes. A number of genes which control PGCs development have been identified in invertebrates, whereas such genes are by and large unelucidated in mammals. Here we describe cloning, genomic structure and expression of mouse homologue of germ cell-less (gcl) gene which is required for PGCs formation in Drosophila. The mouse gcl shows 34% identity compared with Drosophila gcl protein and contains BTB/POZ domain. The gcl gene consists of 14 exons and spans more than 50 kb. The CpG islands are found around exon 1 of the gene. Putative promoter region contains potential binding sites for various transcription factors. Northern blot analysis showed that its mRNA is highly expressed in adult testis with lower expression in ovary, ES (embryonic stem) cells, and various other organs. In situ hybridization analysis revealed strong expression of the gcl gene in the pachytene stage spermatocytes. The expression was also observed in post-migratory PGCs, but was not apparent in migratory and pre-migratory PGCs. Further studies including gene disruption analysis would provide an important insight into mammalian germ lineage development.

Aging↗

PubMed1994

Differential activation of transcription versus recombination of transgenic T cell receptor beta variable region gene segments in B and T lineage cells.

We have tested the ability of the T cell receptor beta (TCR-beta) transcriptional enhancer (E beta) to confer transcriptional activation and tissue-specific V(D)J recombination of TCR-beta V, D, and J segments in a transgenic minilocus recombination substrate. We find that the minimal E beta element, as previously shown for a DNA segment that contained the E mu element, promotes a high level of substrate D to J beta rearrangement in both B and T cells, but only promotes V beta to DJ beta rearrangement in T cells. Thus, both the E mu and E beta elements similarly direct V(D)J recombination of this substrate in vivo, supporting a general role for transcriptional enhancers in the normal regulation of this rearrangement process. Surprisingly, however, we found that both the V beta and DJ beta portion of the constructs were transcribed in an enhancer-dependent fashion (conferred by either E mu or E beta) in both B and T lineage cells, including normal precursor B cells propagated in culture. These findings indicate that, at least in some contexts, transcriptional activation, per se, is not sufficient to confer V(D)J recombinational accessibility to a substrate V gene segment.

Animals↗

PubMed1991

Cell lineage analysis of the gynoecium of maize using the transposable element Ac.

The maize gynoecium develops from a primordium comprising two distinct cell lineages: an epidermal LI and a subepidermal LII lineage. We have analyzed somatic gynoecial sectors marked with red flavonoid pigments by excision of Ac from the P locus. Somatic sector analysis indicates the epidermal lineage starts as a single cell layer at the base of the ovary and thickens into several cell layers, presumably by periclinal divisions, near the silk attachment point. The silk attachment point appears to be mainly an epidermal outgrowth of two of three fused carpels and presumably the silk contains only LI, or mostly LI, with only traces of subepidermal LII cells. The third carpel, covering the germinal face of the kernel, retains a multicellular LII and unicellular LI organization but fails to contribute substantially to stylar outgrowth. Ac transpositions in subepidermal somatic sectors are transmitted to the archesporial cell lineage. Ac transpositions that occur in epidermal sectors are not transmitted to offspring. These results demonstrate that the female megasporocyte is derived from subepidermal (LII) cells.

Clone Cells↗

PubMed2002

A review of inner ear fate maps and cell lineage studies.

A renewed interest in the development of the inner ear has provided more data on the fate and cell lineage relationships of the tissues making up this complex structure. The inner ear develops from a simple ectodermal thickening of the head called the otic placode, which undergoes a great deal of growth and differentiation to form a multichambered nonsensory epithelium that houses the six to nine sensory organs of the inner ear. Despite a large number of studies examining otic development, there have been surprisingly few fate maps generated. The published fate maps encompass four species and range from preotic to otocyst stages. Although some of these studies were consistent with a compartment and boundary model, other studies reveal extensive cell mixing during development. Cell lineage studies have been done in fewer species. At the single cell level the resulting clones in both chicks and frogs appear somewhat restricted in terms of distribution. We conclude that up until late placode stages there are no clear lineage restriction boundaries, meaning that cells seem to mix extensively at these early stages. At late placode stages, when the otic cup has formed, there are at least two boundaries located dorsally in the forming otocyst but none ventrally. These conclusions are consistent with all the fate maps and reconciles the chick and frog data. These results suggest that genes involved in patterning the inner ear may have dynamic and complex expression patterns.

Animals↗

PubMed2000

The human VASA gene is specifically expressed in the germ cell lineage.

To understand the origins and function of the human germ cell lineage and to identify germ cell-specific markers we have isolated a human ortholog of the Drosophila gene vasa. The gene was mapped to human chromosome 5q (near the centromere) by radiation hybrid mapping. We show by Northern analysis of fetal and adult tissues that expression of the human VASA gene is restricted to the ovary and testis and is undetectable in somatic tissues. We generated polyclonal antibodies that bind to the VASA protein in formalin-fixed, paraffin-embedded tissue and characterized VASA protein expression in human germ cells at various stages of development. The VASA protein is cytoplasmic and expressed in migratory primordial germ cells in the region of the gonadal ridge. VASA protein is present in fetal and adult gonadal germ cells in both males and females and is most abundant in spermatocytes and mature oocytes. The gene we have isolated is thus a highly specific marker of germ cells and should be useful for studies of human germ cell determination and function.

Adult↗

PubMed2002

Replication and subnuclear location dynamics of the immunoglobulin heavy-chain locus in B-lineage cells.

The murine immunoglobulin heavy-chain (Igh) locus provides an important model for understanding the replication of tissue-specific gene loci in mammalian cells. We have observed two DNA replication programs with dramatically different temporal replication patterns for the Igh locus in B-lineage cells. In pro- and pre-B-cell lines and in ex vivo-expanded pro-B cells, the entire locus is replicated early in S phase. In three cell lines that exhibit the early-replication pattern, we found that replication forks progress in both directions through the constant-region genes, which is consistent with the activation of multiple initiation sites. In contrast, in plasma cell lines, replication of the Igh locus occurs through a triphasic pattern similar to that previously detected in MEL cells. Sequences downstream of the Igh-C alpha gene replicate early in S, while heavy-chain variable (Vh) gene sequences replicate late in S. An approximately 500-kb transition region connecting sequences that replicate early and late is replicated progressively later in S. The formation of the transition region in different cell lines is independent of the sequences encompassed. In B-cell lines that exhibit a triphasic-replication pattern, replication forks progress in one direction through the examined constant-region genes. Timing data and the direction of replication fork movement indicate that replication of the transition region occurs by a single replication fork, as previously described for MEL cells. Associated with the contrasting replication programs are differences in the subnuclear locations of Igh loci. When the entire locus is replicated early in S, the Igh locus is located away from the nuclear periphery, but when Vh gene sequences replicate late and there is a temporal-transition region, the entire Igh locus is located near the nuclear periphery.

Animals↗

PubMed2003

Specific inhibitor of FGF receptor signaling: FGF-2-mediated effects on proliferation, differentiation, and MAPK activation are inhibited by PD173074 in oligodendrocyte-lineage cells.

Multiple studies have shown that migration, proliferation, and differentiation of oligodendrocyte (OL) lineage cells are influenced by fibroblast growth factor-2 (FGF-2) signaling through its receptors (FGFR) FGFR-1, FGFR-2, and FGFR-3. We report the effectiveness and specificity of a unique inhibitor, PD173074, for inhibiting FGF receptor signaling in OL-lineage cells. Three FGF-mediated responses of OL progenitors and two of differentiated OLs were examined by immunofluorescence microscopy and immunoblotting. PD173074 effectively antagonized the effect of FGF-2 on proliferation and differentiation of OL progenitors in culture. One dose of PD173074 at nanomolar concentrations was sufficient to inhibit ongoing FGF-2 mediated proliferation for prolonged periods, in a non-toxic, dose-dependent manner. In contrast, platelet-derived growth factor (PDGF)-induced proliferation was unaffected by PD173074. Similarly, mitogen-activated protein kinase (MAPK) activation, a downstream event after activation of either FGFR or PDGFR, was also blocked by PD173074 in OL progenitors stimulated with FGF-2 but not PDGF. A general tyrosine kinase inhibitor (PD166285), however, antagonized both FGF-2- and PDGF-mediated responses. PD173074 also completely antagonized two phenotypic alterations of differentiated OLs, specifically downregulation of myelin proteins, and their re-entry into the cell cycle. We conclude that PD173704 is an effective and specific inhibitor for multiple FGF-2-mediated responses of both OL progenitors and differentiated OLs. This inhibitor provides a direct approach for identifying the importance of FGF signaling, comparable in effect to a knockout of all FGF receptors and all FGF ligands, while leaving other pathways unaffected. Thus, PD173704 is an excellent tool for investigating the role of FGF signaling in vivo in the context of combinatorial interactions of other signals.

Animals↗

PubMed2001

Telomerase activity and clinical progression in chronic lymphoproliferative disorders of B-cell lineage.

The activation of telomerase, which specifically occurs in neoplastic cells to avoid telomere attrition at each cell division, is a necessary event in tumorigenesis. The evidence that telomerase is also present in normal B cells at different levels according to their differentiation and activation state makes the study of telomerase activity in B cell tumors particularly interesting. This review summarizes data concerning telomerase activity in chronic lymphoproliferative disorders of B-cell lineage (B-CLD), making suggestions regarding B-cell development and B-cell tumor histogenesis. The role of telomerase activity as a potential prognostic marker, as well as a target of new antineoplastic strategies is discussed.

B-Lymphocytes↗

PubMed1991

Biosynthesis and partial amino acid sequence of the human NDA4 antigen. An activation antigen common to B and T cell lineages.

NDA4, a cell surface protein of molecular mass 46 kDa common to activated peripheral blood B and T cells, plays a unique role in the control of B and T cell maturation. NDA4 inhibits B and T cell activation, as mitogen-stimulated B and T cell blastogenic responses are decreased in the presence of mAb NDA4, the antibody recognizing NDA4. After mitogen-activation, however, the regulatory function of NDA4 changes. Addition of mAb NDA4 to cultures of Staphylococcus aureus Cowan strain A-activated B cells or alloreactive T cell clones stimulates their proliferation. NDA4 epitopes are conserved across primate species lines and are present on transformed cells of neuroectodermal origin. NDA4 is synthesized as a molecular mass 50 kDa precursor and is processed to a mature 46 kDa form within 30 min. The NDA4 Ag also exists as soluble forms of 40 and 42 kDa. The membrane and soluble forms of NDA4 have been purified to homogeneity and sequenced by N-terminal Edman degradation.

Amino Acid Sequence↗

PubMed1994

NUB-7: a stable I-type human neuroblastoma cell line inducible along N- and S-type cell lineages.

Human NB cell lines express features of one or more of three recognizable phenotypes that include N-type (neuroblastic), S-type (Schwannian), and I-type (intermediate phenotype) cells. The I-type cell, which shares properties of both N- and S-type cells, is thought to represent the progenitor cell from which the other two cell types are derived. The MYCN amplified NB cell line NUB-7, established in our laboratory, is now shown to be composed principally of I-type cells. The observed phenotype was stable in culture and was representative of the original surgically resected tumor. The I-type cell designation was established based on morphological characteristics, the coexpression of various N-type (neurofilaments, peripherin, GAP-43, NCAM, MYCN) and S-type cell (vimentin, laminin, fibronectin) markers, and the relatively high level of expression of these markers in comparison to five predominantly N-type, one S-type, and one N/S mixed NB cell lines. Dibutyryl cyclic AMP and retinoic acid induced enhanced expression of N- and S-type phenotypes, respectively, in NUB-7 as supported by specific morphological changes, reduced growth, and changes in the levels of expression of both N- and S-type markers. Our studies with the NUB-7 cell line have now provided convincing evidence for the existence of a bipotential progenitor of N- and S-type cells in NB. As well, the NUB-7 cell line may also represent the tumor counterpart of a sympathetic ganglion progenitor cell.

Bucladesine↗

PubMed1997

Cell lineage and differentiation state are primary determinants of MYCN gene expression and malignant potential in human neuroblastoma cells.

Neuroblastoma cell lines typically exhibit multiple cell phenotypes, counterparts of those comprising the embryonic neural crest. Expression of the MYCN gene, usually amplified in cell lines, differs markedly among the various differentiation phenotypes. Whereas neuroblastic (N-type) and stem cell (I-type) sublines have abundant MYCN RNA and protein, S-type cells (nonneuronal neural crest precursors) have a 4- to 9-fold lower level of cytoplasmic mRNA and a 2- to 36-fold lower protein content. N and S sublines with chromosomally integrated MYCN genes have similar gene copy numbers. Thus, in these S cells, MYCN expression is downregulated. Nuclear run-on and mRNA stability assays have revealed similar transcription rates and mRNA half-lives in N and S cells from two cell lines, indicating that downregulation occurs posttranscriptionally prior to mRNA degradation in the cytoplasm. S-type cells derived from double minute chromosome-containing lines show 4- to 10-fold lower gene copy numbers than N counterparts. Experimental induction of differentiation to neuronal/neuroendocrine or to S-type cells results in a marked reduction of MYCNexpression and, in double minute chromosome-containing N-type sublines, in gene loss as well. Malignant potential as indicated by soft agar growth capacity and tumor formation in nude mice is markedly diminished in S cells and, generally, is directly proportional to MYCN mRNA levels. The most plausible relationship suggested by our data is that MYCN expression, regulated by cell lineage and/or differentiation state, directly modulates the malignant potential of human neuroblastoma cells.

Animals↗

PubMed1985

Improved fluorescent compounds for tracing cell lineage.

In this note simple methods for the synthesis of several new fluorescent cell lineage tracers are described. These are fluorescent dextrans with average molecular weights of approximately 11 X 10(3), and with one or more fluorophore molecules covalently coupled to each dextran chain. These fluorescent dextrans are brighter than commercially obtainable products, and can be microinjected using either air-pressure injection or iontophoresis. They are long-lasting and have a uniform distribution in the cytoplasm of embryonic cells, clearly revealing very fine cell extensions such as cilia, axons, and filipodia. A method is also described for covalently attaching free amino groups to fluorescent dextran to make the tracers cofixable with cellular constituents by aldehyde treatment. Fluorescent dextran-amine tracers allow embryonic cell lineages to be studied in fixed, permeabilized, or sectioned embryos.

Amines↗

PubMed2001

Ulcer associated cell lineage glands expressing trefoil peptide genes are induced by chronic ulceration in ileal pouch mucosa.

BACKGROUND: Chronic ulcerative conditions in the gastrointestinal tract result in the appearance of the ulcer associated cell lineage (UACL). The glands of this new cell lineage secrete epidermal growth factor, transforming growth factor alpha, and the trefoil factor family (TFF) peptides, which are known to participate in repair processes. Pouchitis is the most frequent complication of ileal pouch-anal anastomosis. AIM: Our aim was to determine whether the mucosal ulceration present in pouchitis can induce the development of UACL glands. METHODS: Biopsies from ileal pouches with pouchitis (n=10), healthy pouches (n=5), and normal terminal ileum (n=5) were studied. Expression of TFF mRNA was assessed by in situ hybridisation. TFF1 and TFF2 proteins were localised by immunochemistry. RESULTS: UACL glands containing TFF1 and TFF2 were observed in six patients with pouchitis. In some glands, there was TFF3 mRNA as has been reported for Crohn's UACL. None of the biopsies from ileal reservoirs without pouchitis showed UACL glands (p<0.05). Neither TFF1 nor TFF2 expression was detected in ileal reservoirs without pouchitis. CONCLUSION: UACL glands arise de novo in ileal pouch mucosa of patients with pouchitis and express all three TFF peptide genes. Chronic inflammation alone, present in healthy pouches, is not enough to stimulate the growth of the UACL, and additional stimuli consequent on ulceration may be needed.

Autoradiography↗

PubMed1990

Cell lineage markers in human pancreatic cancer.

The normal pancreas consists of three major cell types or lineages that share a common embryologic origin from pluripotent endodermal precursors. The type of cell that undergoes neoplastic transformation to form a pancreatic carcinoma is controversial and may influence the phenotype and biologic behavior of the tumor. In this study, immunohistologic techniques were used to determine the cell lineage differentiation expressed in 29 primary exocrine pancreatic adenocarcinomas, five metastatic exocrine pancreatic adenocarcinomas, and five islet cell neoplasma. Specimens of normal pancreas and chronic pancreatitis were used for comparison. The cell lineage markers consisted of monoclonal and polyclonal antibodies against trypsin and lipase (acinar cells); secretory component, carbonic anhydrase II, and pancreatic cancer mucin SPan-1 (ductal cells); and chromogranin-A and somatostatin (islet cells). The expression of carcinoembryonic antigen (CEA) and lysozyme were also determined. This collection of markers allowed the differentiation between acinar, ductal, and islet cells of normal pancreas and chronic pancreatitis specimens. The expression of cell lineage markers in islet cell tumors was homogeneous and restricted to chromogranin-A. In contrast, the expression of these markers in primary and metastatic exocrine pancreatic adenocarcinomas was variable. Reactivity with monoclonal anti-CEA was absent in normal pancreas, and was present in 83% of chronic pancreatitis specimens as well as 90% of exocrine pancreatic adenocarcinomas. In addition, lysozyme reactivity was absent in normal pancreas; however, lysozyme was expressed in one case of chronic pancreatitis, 17 cases of primary carcinoma, and three cases of metastatic carcinoma. These findings support the concept that the original transformed cell type in many pancreatic exocrine carcinomas resemble endodermal "stem cells" that retain the capability of differentiation along more than one cell lineage pathway.

Biomarkers↗