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At least 1,279 records · Page 71Linked to original sources
PubMed1999

Bovine monocytoid cells transformed to proliferate cease to exhibit lineage-specific functions.

Bovine cell lines of the monocyte-Mphi lineage were tested for surface marker expression and were characterized with respect to functions. Cell lines tested encompassed an SV40-transformed cell line (Bo-Mac), a spontaneously emerging monocytoid cell line (M617), and T. annulata-transformed lines derived from bovine Mphi. All lines failed to express surface markers expressed by 1 degrees Mphi, with the exception of CD44, WC9 and the DH59 myleoid cell marker. T. annulata-derived lines expressed, in addition, CD45 and MHC-class-II molecules. Except for nonspecific esterase staining, none of the typical macrophage functions were expressed by any of the cell lines. These included phagocytosis of opsonized E. coli bacteria and of IgG-treated erythrocytes, eliciting of an oxidative burst, the ability to express type-I-interferon (IFN) and to respond to lipopolysaccharide, as determined by four different effector functions (nitric oxide synthesis, tumor necrosis factor (TNF) secretion, IFN production and procoagulant activity upregulation). When transformation induced by T. annulata was reversed by chemical elimination of the parasite, cells ceased to proliferate but started to acquire some of the phenotypic characteristics of Mphi. This suggests that regardless of their origin, exponentially growing bovine cells of the monocyte-Mphi lineage poorly represent a lineage-specific phenotype and should be used with caution in immunological studies.

Animals↗
PubMed1996

DNA markers define two major phylogenetic lineages of Trypanosoma cruzi.

Parasitic protozoa within the taxon Trypanosoma cruzi are considered to be derived from multiple clonal lineages, and show broad genetic diversity as a result of propagation with little or no genetic exchange. We have analyzed a wide sample of T. cruzi isolates from vertebrate and invertebrate hosts by PCR amplification of a ribosomal RNA gene sequence, a mini-exon gene sequence and random amplified polymorphic DNA (RAPD). Amplification of the distinct rDNA and mini-exon gene sequences indicated a dimorphism within both of the tandemly-repeated genes: 125 or 110 bp products for rDNA and 300 or 350 bp products for the mini-exon. Within individual isolates, one of three associations was observed: the 125 bp rDNA product with the 300 bp mini-exon product (defined as group 1), the 110 bp rDNA product with the 350 bp mini-exon product (defined as group 2) and the presence of both rDNA amplification products with the mini-exon group 1 product (group 1/2). The RAPD analysis showed variability between individual isolates, however, tree analysis clearly indicated the presence of two major branches. Interestingly, the rDNA/mini-exon group 2 isolates correlated precisely with one branch of the RAPD-derived tree; group 1 and group 1/2 isolates correlated with the other branch. Our studies show a clear division of T. cruzi into two major lineages presenting a high phylogenetic divergence. Hypotheses are discussed to explain the origin of the two lineages as well as isolates that are hybrid for group 1 and 2 rDNA markers.

Animals↗
PubMed1997

Speculation on possible life cycles for the clonal lineages in the genus toxoplasma.

Recent evidence suggests that the strains currently classified in the genus Toxoplasma, ie. within the species Toxoplasma gondii, may actually comprise at least two clonal lineages correlated with their virulence in mice. Here, Alan Johnson reviews these data in the context of evolution and speciation within the genus, and raises hypotheses on how the virulent lineage may undergo an asexual life cycle in nature, similar to that found for the very closely related coccidian, Neospora camnum. The putative vertical transmission life cycle of this mouse virulent lineage of T. gondii could involve passage to the foetus late in pregnancy, or transmission in milk to the neonate after birth.

Journal Article↗
PubMed2001

The 49a,f haplotype 11 is a new marker of the EU19 lineage that traces migrations from northern regions of the Black Sea.

Previous studies on human Y-chromosome polymorphisms in the European populations highlighted the high frequency of the 49a,f/TaqI haplotype 11 and of the Eu19 (M17) lineage in Eastern Europe. To better understand the origin and the evolution of the Eu19, and its relationship with 49a,f Ht11, this study surveyed 2,235 individuals (mainly from Europe and the Middle East) for the 49a,f Ht11 and for many biallelic markers defining the Eu19 lineage. As previously described, the highest frequency of Eu19 was found in Eastern Europe. All the Eu19 Y-chromosomes turned out to be 49a,f Ht11 or its derivatives, the distribution of which suggests that the Eu19/49a,f Ht11 emerged in Ukraine, probably in a Palaeolithic population. Thereafter, the spread of this lineage toward Europe, Asia, and India occurred at different waves over a few thousands years. At present this seems to indicate the influence of the Ukraine Palaeolithic groups in the gene pool of modern populations. For the first time it is possible to make inferences about the evolution of some haplotypes of the 49a,f system. In spite of its unknown molecular base, this is one of the first most informative polymorphisms of the Y chromosome.

Alleles↗
PubMed2001

Tissue source dictates lineage outcome of human fetal CD34(+)CD38(-) cells.

OBJECTIVE: The translocation from fetal liver hematopoiesis to secondary organs occurs during the second trimester of human gestation. It has been hypothesized that stem cells migrate and acquire lineage potential based on cues specific to the adopted microenvironment. We evaluated primitive hematopoietic cell populations in the fetal human to determine if lineage restriction precedes or follows translocation to sites of hematopoietic activity including thymus, spleen, bone marrow, and liver. METHODS: Sets of hematopoietic tissues from individual second-trimester human abortuses were used to compare and quantitate the lineage outcome of immunophenotypically primitive cells from each of the hematopoietic organs using ex vivo myeloid and lymphoid differentiation systems. RESULTS: Despite uniformity in immunophenotype, functional capabilities were highly restricted by the tissue of origin and alteration in the ex vivo differentiation context did not lead to a change in differentiation outcome. CONCLUSION: Translocation of primitive cells from fetal liver to tissues of mature hematopoietic activity is associated with tissue-specific, quantitative changes in differentiation potential that are unresponsive to alternative differentiation environments. These data suggest that multipotentiality is lost prior to or upon stem-cell migration in the developing human. It is not persistent with residence in a secondary hematopoietic organ.

ADP-ribosyl Cyclase↗
PubMed1999

Measles virus nucleocapsid transcript expression is not restricted to the osteoclast lineage in patients with Paget's disease of bone.

Abundant evidence supports a viral etiology for Paget's disease of bone (PD), however, an infectious virus has not been isolated from PD patients. Thus, it is unclear how the virus is maintained for the many years that the disease persists in patients. We considered if a primitive multipotential hematopoietic stem cell (HSC), which is self-renewing, passes the virus to its differentiated progeny and serves as a reservoir for the pathogen. If a primitive stem cell harbored measles virus (MV), then other hematopoietic lineages derived from this stem cell in PD patients should also express MV transcripts. Therefore, because the human hematopoietic stem cell has not been clearly identified or isolated in large numbers, we isolated RNA from highly purified erythroid and multipotential hematopoietic progenitors that are the precursors for erythroid, granulocyte, megakaryocyte and macrophages (CFU-GEMM), and used RT-PCR to determine if MV nucleocapsid transcripts were present. MV transcripts were detected in PD patients in early erythroid (BFU-E) and more primitive multipotential myeloid progenitors (CFU-GEMM). Nonhematopoietic stromal cells from PD patients did not express MV transcripts. The expression of MV transcripts in erythroid progenitors was further confirmed by in situ hybridization using antisense riboprobes to MV nucleocapsid transcripts. Thus, our findings suggest that the pluripotent HSCs may be a potential reservoir for the virus. We propose that when HSCs, which contain MV, divide they produce a second HSC that serves as a reservoir for the virus and also transmit the virus to their more differentiated progeny in the erythroid and myeloid lineages. This mechanism would permit a defective virus to persist in HSCs of PD patients for many years, since HSCs are usually in G0 phase, and then be transmitted to more differentiated cells. This model further suggests that a mature complete virus that affects cell function could only act pathogenetically in the osteoclast lineage, which offers a permissive milieu.

Antigens, CD34↗
PubMed2002

Identification and characterization of a novel member of olfactomedin-related protein family, hGC-1, expressed during myeloid lineage development.

We have cloned a novel hematopoietic granulocyte colony-stimulating factor (G-CSF)-induced olfactomedin-related glycoprotein, termed hGC-1 (human G-CSF-stimulated clone-1). mRNA differential display was used in conjunction with a modified two-phase liquid culture system. Cultures were enriched for early precursors of erythroid, myeloid, and megakaryocytic lineages, which were isolated after induction with erythropoietin, G-CSF, and thrombopoietin, respectively. RNA from the enriched cells was subjected to differential display analysis to identify lineage-specific expressed genes. One clone specifically induced by G-CSF, hGC-1, was characterized. The 2861 bp cDNA clone of hGC-1 contained an open reading frame of 1530 nucleotides, translating into a protein of 510 amino acids with a signal peptide and six N-linked glycosylation motifs. The protein sequence of hGC-1 showed it to be a glycoprotein of the olfactomedin family, which includes olfactomedin, TIGR, Noelin-2 and latrophilin-1. Olfactomedin-like genes show characteristic tissue-restricted patterns of expression; the specific tissues expressing these genes differ among the family members. hGC-1 was strongly expressed in the prostate, small intestine, and colon, moderately expressed in the bone marrow and stomach, and not detectable in other tissues. In vitro translation and ex vivo expression showed hGC-1 to be an N-linked glycoprotein. The hGC-1 gene locus mapped to chromosome 13q14.3. Together, our findings indicate that hGC-1 is primarily expressed as an extracellular olfactomedin-related glycoprotein during normal myeloid-specific lineage differentiation, suggesting the possibility of a matrix-related function for hGC-1 in differentiation.

Amidohydrolases↗
PubMed2003

Human-specific subfamilies of HERV-K (HML-2) long terminal repeats: three master genes were active simultaneously during branching of hominoid lineages.

Using 40 known human-specific LTR sequences, we have derived a consensus sequence for an evolutionary young HERV-K (HML-2) LTR family, which was named the HS family. In the human genome the HS family is represented by approximately 150-160 LTR sequences, 90% of them being human-specific (hs). The family can be subdivided into two subfamilies differing in five linked nucleotide substitutions: HS-a and HS-b of 5.8 and 10.3 Myr evolutionary ages, respectively. The HS-b subfamily members were transpositionally active both before the divergence of the human and chimpanzee ancestor lineages and after it in both lineages. The HS-a subfamily comprises only hs LTRs. These and other data strongly suggest that at least three "master genes" of HERV-K (HML-2) LTRs were active in the human ancestor lineage after the human-chimpanzee divergence. We also found hs HERV-K (HML-2) LTRs integrations in introns of 12 human genes and identified 13 new hs HERV-K (HML-2) LTRs.

Animals↗
PubMed1997

Generation of cell diversity in the peripheral autonomic nervous system: the sympathoadrenal cell lineage revisited.

Based on recent evidence from in vitro and gene knock-out/knock-in studies this short review summarizes the molecular scenario underlying the development of autonomic neurons from the neural crest. The focus is on the sympathoadrenal (SA) cell lineage. While migrating ventrally precursors of this cell lineage are exposed to signals from notochord/ventral neural tube probably including the protein sonic hedgehog. These and signals in the region of the dorsal aorta (members of the family of bone morphogenetic proteins), where SA progenitor cells subsequently assemble, are essential for the induction of the adrenergic phenotype. SA progenitor cells subsequently differentiate into paravertebral and prevertebral sympathetic neurons, intra- and extra-adrenal chromaffin cells and intermediate SIF (small intensely fluorescent) cells. Based on in vitro studies with isolated SA and chromaffin progenitor cells glucocorticoids have been claimed as essential for suppressing a neuronal commitment and channeling SA cells towards the chromaffin phenotype. Unexpectedly, mice deficient for a functional glucocorticoid receptor possess the full complement of adrenal chromaffin cells at birth. We present a hypothetical scenario consistent with these data, in which chromaffin cell development would be the default pathway in the SA cell lineage, while development into a neuronal direction requires specific growth factor signaling, which is probably distinct for paravertebral and prevertebral sympathetic neurons.

Animals↗
PubMed1997

An enhancer that directs lineage-specific expression of CD8 in positively selected thymocytes and mature T cells.

Positive selection of CD4+CD8+ T cells to the CD4+CD8- helper and CD4- CD8+ cytotoxic lineages is a multistep process that involves complex regulation of coreceptor gene expression. By analyzing expression of a reporter gene in transgenic mice, we have identified a DNA segment, located between the murine CD8beta and CD8alpha genes, that has enhancer activity restricted to CD8 lineage cells. Remarkably, this enhancer functions in thymocytes undergoing positive selection to the CD4-CD8+ phenotype but not in immature double-positive thymocytes. The enhancer also functions in gut intraepithelial lymphocytes that express CD8alpha but not CD8beta, suggesting that it is specific for CD8alpha expression. The tight correlation between activation of this enhancer and the final step in positive selection has important implications for understanding the mechanism of lineage commitment in thymocytes.

Animals↗
PubMedDate not supplied

Cbf beta is involved in maturation of all lineages of hematopoietic cells during embryogenesis except erythroid.

The transcription factor Cbf beta forms a heterodimeric complex with members of the Runx family of proteins. Together, Cbf beta and Runx1 play a critical role in the establishment of definitive hematopoiesis in mouse embryos. Previously, we used a Cbfb-GFP "knock-in" mouse model to demonstrate that Cbf beta is expressed in hematopoietic stem cells of the mouse fetal liver and aorta-gonad-mesonephros (Blood 100 (2002), 2449). We also examined the expression pattern of Cbf beta in different lineages of adult hematopoietic cells and found that it is expressed uniformly in all lineages except B lymphocytes and erythroid cells. Cbf beta expression decreases during maturation of B cells in the adult bone marrow, and is not expressed in nucleated erythroid precursors. Here, we examine the expression of Cbf beta in various hematopoietic lineages, including myeloid, lymphoid, and erythroid during late stages of embryonic development, and compare it to the pattern observed in adults. We find that there are subtle differences in expression of Cbf beta-GFP in embryonic hematopoietic cells compared to their adult counterparts, but that the overall pattern is the same. Our data complement recently published data on hematopoetic defects observed in transgenic Cbfb-null mouse embryos partially rescued by ectopic expression of Cbfb (Nature Genet. 32 (2002), 633; Nature Genet. 32 (2002), 645). and supports the emerging view that Cbf beta and Runx proteins are required for normal maturation of hematopoietic cells as well as establishment of definitive hematopoiesis.

Animals↗
PubMed2004

Candidate lineage marker genes in human preimplantation embryos.

Cell allocation and subsequent lineage commitment in the human embryo may be established as early as in the unfertilized oocyte. This phenomenon might be the result of subtle differences of gene expression and protein distribution. To assess whether gene expression profiling by reverse transcription-polymerase chain reaction could be a suitable tool for the detection of cell allocation and lineage commitment, the expression pattern of the putative inner cell mass marker gene Oct-4 and the trophectodermal marker genes beta-HCG and beta-LH were correlated in individual blastomeres of preimplantation human embryos. In 2- to 5-cell stage embryos, expression of beta-HCG and Oct-4 mRNA was negatively correlated in all blastomeres with statistical significance, suggesting that cell allocation can be assessed by those markers at early stages. In 7- to 10-cell stage embryos, expression of beta-LH and Oct-4 mRNA was negatively correlated in some blastomeres without statistical significance, suggesting that more experiments are necessary to decide if lineage commitment can be assessed in some cells by those markers at later stages.

Blastocyst↗
PubMed2006

PCR-based screening and lineage identification of Trypanosoma cruzi directly from faecal samples of triatomine bugs from northwestern Argentina.

This study applied improved DNA extraction and polymerase chain reaction strategies for screening and identification of Trypanosoma cruzi lineages directly from faeces of triatomines collected in a well-defined rural area in northwestern Argentina. Amplification of the variable regions of the kinetoplastid minicircle genome (kDNA-PCR) was performed in faecal lysates from 33 microscope (MO)-positive and 93 MO-negative Triatoma infestans, 2 MO-positive and 38 MO-negative Triatoma guasayana and 2 MO-positive and 73 MO-negative Triatoma garciabesi. kDNA-PCR detected T. cruzi in 91% MO-positive and 7.5% MO-negative T. infestans, which were confirmed by amplification of the minicircle conserved region. In contrast, kDNA-PCR was negative in all faecal samples from the other triatomine species. A panel of PCR-based genomic markers (intergenic region of spliced-leader DNA, 24Salpha and 18S rRNA genes and A10 sequence) was implemented to identify the parasite lineages directly in DNA lysates from faeces and culture isolates from 28 infected specimens. Two were found to be infected with TCI, 24 with TCIIe, 1 with TCIId and 1 revealed a mixed TCI+TCII infection in the faecal sample whose corresponding culture only showed TCII, providing evidence of the advantages of direct typing of biological samples. This study provides an upgrade in the current diagnosis and lineage identification of T. cruzi in field-collected triatomines and shows T. cruziII strains as predominant in the region.

Animals↗
PubMed1999

Levels of virulence are not determined by genomic lineage of Salmonella enterica serotype Enteritidis strains.

Mouse virulence and the ability to adhere to, and invade cultured MDCK cells were investigated in 38 phage type reference strains of Salmonella enterica serotype Enteritidis and correlated with genomic lineage. The genomic lineage of 11 of the strains was determined in the present study; one IS200 and one ribotype pattern that had not been reported previously were observed. Log c.f.u. in the spleen 10 days post intraperitoneal (i.p.) infection with 3x10(3) bacteria (logVC10) varied between 2.9 and 8.7. The reference strains of PT7 and PT23 were found to be semi-rough and were of low virulence. All other strains possessed smooth LPS. Within each of the two major clonal lines, as well as among phage types outside these, both highly virulent and moderate to low virulent strains were present. While all strains of PT1, PT2 and PT8 were highly virulent, low virulent strains were detected in PT4 and PT13. The ability to adhere to, and invade MDCK cells varied between phage types (adherence between 13 and 61% of the inocula and invasion between 4 and 151% of the adherent cells). The results of the cell culture experiments did not correlate with the results of mouse virulence tests. No correlation between clonal lineage and virulence was found within S. Enteritidis. It seems most likely that some strains have lost some of the essential factors enabling this serotype to cause successful systemic infection.

Animals↗
PubMed2005

Towards a phylogenetic classification of Cordyceps: ITS nrDNA sequence data confirm divergent lineages and paraphyly.

The ascomycetous genus Cordyceps accommodates endoparasitic species that attack arthropods or other fungi. Analyses of ITS nrDNA sequence data of 72 taxa from the teleomorph genera Cordyceps, Claviceps, Epichloë, and the anamorph genera Akanthomyces, Beauveria, Metarhizium, Hirsutella, Hymenostilbe, Paecilomyces, Polycephalomyces, and Tolypocladium assigned the taxa to four main evolutionary lineages not reflected in the current classification of Cordyceps. Ten subclades were recognized from separate analyses of data subsets. Judged from the ITS phylogenies, Cordyceps spp. with branched stromata were highly supported as a divergent lineage. Host specificity was found to be of limited phylogenetic significance, and several host shifts are suggested to have occurred during the evolution of Cordyceps. Similar ascospore morphology was not reflected in the phyletic groups, and closely related taxa showed large interspecific variation with respect to the number of segments in which the ascospores are divided. However, combinations of selected characters were found to delimitate some lineages, e.g. all Cordyceps spp. that attack hosts in the insect orders Coleoptera and Lepidoptera, and with non-immersed perithecia and clavate to acicular, brightly yellowish to reddish stromata, constituted a separate clade. Furthermore, all Cordyceps spp. with perithecia obliquely immersed in the stroma were recognized as a distinct monophyletic group. This clade is additionally characterized by the formation of anamorphs ascribable to the genus Hymenostilbe. The mycogenous Cordyceps spp. grouped in a separate subclade, interspersed by two cicadaen parasites and all Tolypocladium spp. except T. parasiticum. Tolypocladium and Beauveria were found to be polyphyletic. The included Claviceps and Epichloë taxa appeared to be derived within Cordyceps, thus making Cordyceps paraphyletic as suggested in other studies.

Cordyceps↗
PubMed1999

Pit-1 positive alpha-subunit positive nonfunctioning human pituitary adenomas: a dedifferentiated GH cell lineage?

Pit-1 is a transcription factor which has been reported to regulate differentiation toward GH, PRL and TSH in the anterior pituitary glands. In the human pituitary adenomas, Pit-1 is highly expressed in GH secreting and TSH secreting adenomas as it can well be anticipated. Interestingly, human non-functioning pituitary adenomas also express Pit-1, especially it was expressed in all alpha SU positive nonfunctioning adenomas. The human anterior pituitary cells are special in comparison with rodents in a finding that alpha SU is frequently colocalized with GH. As alpha SU is the first hormone appearing during fetal development in the rodent pituitary glands, it may be postulated that alpha SU Pit-1 positive cells undergo differentiation in the GH cell lineage. From this background, this paper proposes that "alpha SU positive Pit-1 Positive" cells are the ones in the GH cell lineage, more specifically a dedifferentiated cell lineage toward alpha SU/GH/Pit-1.

Adenoma↗
PubMed2002

Mixed lineage kinase 3 inhibits phorbol myristoyl acetate-induced DNA synthesis but not osteopontin expression in rat mesangial cells.

Mixed lineage kinase 3 (MLK 3) (also called SPRK or PTK-1) is a recently described member of the family of the mixed lineage kinase subfamily of Ser/Thr protein kinases that interacts with mitogen-activated protein kinase pathways. In order to test the biological relevance and potential interaction of MLK 3 with protein kinase C-mediated signaling pathways, human MLK 3 was stably expressed in rat glomerular mesangial cells using a retroviral vector (LXSN) and the effects of phorbol myristoyl acetate (PMA) on DNA synthesis and osteopontin mRNA expression were examined. In control (vector-transfected) mesangial cells PMA increased [3H]-thymidine incorporation in a concentration-dependent manner. In mesangial cells stably expressing MLK 3, the PMA-induced increase in [3H]-thymidine incorporation was significantly reduced (> 50%). However, the PMA-induced increase in osteopontin mRNA was not affected by MLK 3 expression. To determine the mechanisms of these effects, activation of ERK2, JNK1 and p38 in response to PMA was examined in both vector and MLK 3 transfected cells. ERK2 activation was increased several fold by PMA in control cells but was attenuated significantly in MLK 3 expressing cells, suggesting that MLK 3 expression in mesangial cells can negatively regulate the ERK pathway. PMA had no significant effect on JNK and P38 activation, in either vector- or MLK 3-expressing cells. PD98059, a MEK inhibitor blocked PMA-induced DNA synthesis without affecting osteopontin expression. These results suggest that while protein kinase C activation increases cellular proliferation and osteopontin mRNA expression, over-expression of MLK 3 affects only the PKC-induced DNA synthesis, probably through inhibition of ERK. These results also indicate a novel mechanism of growth regulation by a member of the mixed-lineage kinase family that might have significant therapeutic implications in proliferative glomerulonephritis.

Animals↗
PubMedDate not supplied

Cell lineage-specific undermethylation of mouse repetitive DNA.

Several distinct cell lineages are established during mouse embryogenesis. The trophectoderm and primitive endoderm give rise to extraembryonic structures alone, while the primitive ectoderm becomes the fetus proper. Recent studies suggest that the levels of DNA modification are lower in inactive X chromosomes from extraembryonic tissues than in embryonic and adult somatic tissues. Using HpaII/MspI isoschizomers, Southern blots and cloned probes, we show here that repetitive DNA sequences from all derivatives of the two extraembryonic lineages, trophectoderm and primitive endoderm, are substantially undermethylated compared with primitive ectoderm derivatives. This contrasts with the highly methylated state of these repetitive elements observed in adult somatic tissues. Specific demethylation or inhibition of de novo methylation, or a combination of both mechanisms, may be involved. These findings suggest that elements of gene regulation dependent on DNA modification may be different in extraembryonic cell lineages.

Animals↗