Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Lineage”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed2001

Within the hemopoietic system, LAR phosphatase is a T cell lineage-specific adhesion receptor-like protein whose phosphatase activity appears dispensable for T cell development, repertoire selection and function.

Expression of the receptor-type tyrosine phosphatase LAR was studied in cells of the murine hemopoietic system. The gene is expressed in all cells of the T cell lineage but not in cells of any other hemopoietic lineage and the level of expression in T cells is developmentally regulated. The CD4(-)8(-)44(+) early thymic immigrants and mature (CD4(+)8(-)/CD4(-)8(+)) thymocytes and T cells express low levels, whereas immature (CD4(-)8(-)44(-) and CD4(+)8(+)) thymocytes express high levels of LAR. Among bone marrow cells only uncommitted c-kit(+)B220(+)CD19(-) precursors, but not B cell lineage committed c-kit(+)B220(+)CD19(+) precursors, express low levels of LAR. In contrast to the c-kit(+)B220(+)CD19(+) pre-BI cells from normal mice, counterparts of pre-BI cells from PAX-5-deficient mice express LAR, indicating that PAX-5-mediated commitment to the B cell lineage results in suppression of LAR. During differentiation of PAX-5-deficient pre-BI cell line into non-T cell lineages, expression of LAR is switched off, but it is up-regulated during differentiation into thymocytes. Thus, within the hemopoietic system, LAR appears to be a T cell lineage-specific receptor-type phosphatase. However, surprisingly, truncation of its phosphatase domains has no obvious effect on T cell development, repertoire selection or function.

Amino Acid Sequence↗
PubMed1997

Distinct neuronal lineages of the ascidian embryo revealed by expression of a sodium channel gene.

The ascidian larva contains tubular neural tissue, one of the prominent anatomical features of the chordates. The cell-cleavage pattern and cell maps of the nervous system have been described in the ascidian larva in great detail. Cell types in the neural tube, however, have not yet been defined due to the lack of a suitable molecular marker. In the present work, we identified neuronal cells in the caudal neural tube of the Halocynthia embryo by utilizing a voltage-gated Na+ channel gene, TuNa I, as a molecular marker. Microinjection of a lineage tracer revealed that TuNa I-positive neurons in the brain and in the trunk epidermis are derived from the a-line of the eight-cell embryo, which includes cell fates to epidermal and neural tissue. On the other hand, TuNa I-positive cells in the more caudal part of the neural tissue were not stained by microinjection into the a-line. These neurons are derived from the A-line, which contains fates of notochord and muscle, but not of epidermis. Electron microscopic observation confirmed that A-line-derived neurons consist of motor neurons innervating the dorsal and ventral muscle cells. Isolated A-line blastomeres have active membrane excitability distinct from those of the a-line-derived neuronal cells after culture under cleavage arrest, suggesting that the A-line gives rise to a neuronal cell distinct from that of the a-lineage. TuNa I expression in the a-line requires signals from another cell lineage, whereas that in the A-line occurs without tight cell contact. Thus, there are at least two distinct neuronal lineages with distinct cellular behaviors in the ascidian larva: the a-line gives rise to numerous neuronal cells, including sensory cells, controlled by a mechanism similar to vertebrate neural induction, whereas A-line cells give rise to motor neurons and ependymal cells in the caudal neural tube that develop in close association with the notochord or muscle lineage, but not with the epidermal lineage.

Animals↗
PubMed1998

Late specification of Veg1 lineages to endodermal fate in the sea urchin embryo.

Single blastomeres of the sixth-cleavage veg1 and veg2 tiers of Strongylocentrotus purpuratus embryos were labeled with DiI lineage tracer, and the disposition of the progeny was followed through the blastula and gastrula stages in order to determine their respective endodermal and ectodermal contributions. In the endoderm of postgastrula embryos, veg1-derived cells constituted nearly all of the prospective hindgut and about half of the prospective midgut, while veg2-derived cells made up the prospective foregut and half the midgut. Oral veg1 clones consistently contributed more cells to endoderm than aboral veg1 clones. Oral veg1 clones extended along the archenteron up to the foregut region, while aboral veg1 clones contributed only small numbers of hindgut cells but large patches of ectoderm cells that extended out to the prospective larval vertex. The oral/aboral asymmetry in veg1 allocations was also demonstrated using chimeric embryos, the animal halves of which were labeled with a rhodamine-dextran. Lineages expressing the vegetal plate marker Endo16 were more precisely determined by combining lineage tracer injection with whole-mount in situ hybridization. Endo16 expression was found in all cells that are going to participate in gastrulation. Recruitment of new cells to the Endo16 domain occurs in advance of the actual invagination of those cells. During the blastula stages Endo16 expression expands radially until all cells in the veg2 lineages express this gene. The first phase of gastrulation, including the normal buckling of the vegetal plate and primary invagination of the archenteron, involves only the Endo16-expressing cells of the veg2 lineages. As the archenteron begins to elongate, marking the onset of the second phase of gastrulation, there is an asymmetric expansion of Endo16 into the veg1-derived cells that will contribute to the hindgut and midgut in accordance with lineage tracing observations. The results indicate a relatively late specification of veg1-derived cells, resulting in late recruitment to the periphery of the vegetal plate territory as gastrulation proceeds. Differential recruitment of veg1-derived cells on the oral side of the embryo introduces an oral bias to gastrulation by disproportionately increasing the number of cells on the oral side that are competent to participate in gastrulation.

Animals↗
PubMed2002

Cell lineage, axis formation, and the origin of germ layers in the amphipod crustacean Orchestia cavimana.

Embryos of the amphipod crustacean Orchestia cavimana are examined during cleavage, gastrulation, and segmentation by using in vivo labelling. Single blastomeres of the 8- and 16-cell stages were labelled with DiI to trace cell lineages. Early cleavage follows a distinct pattern and the a/p and d/v body axes are already determined at the 4- and 8-cell stages, respectively. In these stages, the germinal rudiment and the naupliar mesoderm can be traced back to a single blastomere each. In addition, the ectoderm and the postnaupliar mesoderm are separated into right and left components. At the16-cell stage, naupliar ectoderm is divided from the postnaupliar ectoderm, and extraembryonic lineages are separated from postnaupliar mesoderm and endoderm. From our investigation, it is evident that the cleavage pattern and cell lineage of Orchestia cavimana are not of the spiral type. Furthermore, the results of the labelling show many differences to cleavage patterns and cell lineages in other crustaceans, in particular, other Malacostraca. The cleavage and cell lineage patterns of the amphipod Orchestia are certainly derived within Malacostraca, whose ancestral cleavage mode was most likely of the superficial type. On the other hand, Orchestia exhibits a stereotyped cell division pattern during formation and differentiation of the germ band that is typical for malacostracans. Hence, a derived (apomorphic) early cleavage pattern is the ontogenetic basis for an evolutionarily older cell division pattern of advanced developmental stages. O. cavimana offers the possibility to trace the lineages and the fates of cells from early developmental stages up to the formation of segmental structures, including neurogenesis at a level of resolution that is not matched by any other arthropod system.

Animals↗
PubMed2004

Lineage development and polar asymmetries in the peri-implantation mouse blastocyst.

The early events of mouse embryogenesis lead to the formation of three distinct cell lineages by the blastocyst: the pluripotent epiblast and the two extraembryonic lineages, the trophoblast and primitive endoderm. Segregation of the lineages depends on the relative levels of expression of key transcription factors, whose localized expression must be controlled by the earlier events of compaction and polarization of the morula. Soon after lineage specification, the two extraembryonic lineages show evidence of early polarities that may relate to the polarity of the postimplantation embryo at gastrulation. The exact relationship between lineage segregation, preimplantation polarities and the postimplantation axes remain to be determined but are now open to molecular and cellular investigation.

Animals↗
PubMed2004

Identification of lineage-specific zygotic transcripts in early Caenorhabditis elegans embryos.

During Caenorhabditis elegans embryogenesis, a maternally supplied transcription factor, SKN-1, is required for the specification of the mesendodermal precursor, EMS, in the 4-cell stage embryo. When EMS divides, it gives rise to a mesoderm-restricted precursor, MS, and an endoderm-restricted precursor, E. To systematically identify genes that function as key regulators of MS and/or E-derived tissues, we identified, by microarray analyses, genes that are newly transcribed within a short developmental window (approximately 30 min) encompassing the generation and fate specification of the MS and E blastomeres. By comparing total cDNAs generated from individual, carefully staged embryos, we identified 275 genes up-regulated in 12-cell embryos compared to 4-cell embryos. Fifty of these 275 genes are down-regulated in 12-cell skn-1 mutant embryos and are designated skn-1-dependent zygotic (sdz) genes. The spatial and temporal expression patterns in C. elegans embryos of 10 randomly selected sdz genes were analyzed by a nuclear GFP reporter driven by the endogenous 5' regulatory sequence of each gene. GFP expression, although absent at the 4-cell stage, was detected at the 12- to 16-cell stage for all 10 genes and was restricted to EMS-derived lineages for 7 of the 10. Among the seven lineage-specific genes, three genes are expressed equally in both MS and E lineages, two are expressed exclusively or predominantly in the MS lineage, and two are expressed exclusively in the E lineage. Depletion of skn-1 by RNAi abolishes the expression of all seven reporter transgenes in vivo, confirming that these genes are indeed skn-1 dependent. These results demonstrate the successful combination of single-staged embryo cDNAs, genetic mutants, and whole transcriptome microarray analysis to identify stage- and lineage-specific transcripts in early C. elegans embryos.

Animals↗
PubMed2002

Duration of calcineurin and Erk signals regulates CD4/CD8 lineage commitment of thymocytes.

CD4/CD8 lineage commitment of thymocytes is controlled by the T cell receptor-mediated signals and is mimicked in vitro by a long-pulse stimulation of isolated CD4(+)CD8(+) thymocytes with proper combinations of phorbol myristate acetate and the calcium ionophore ionomycin. CD4 lineage commitment required higher intracellular Ca(2+) levels than CD8 lineage commitment in this culture system. The calcineurin inhibitor FK506 at 1nM inhibited the development of thymocytes to either lineage, but 0.3nM FK506 significantly switched the development from the CD4 cell fate to the CD8 cell fate. The switch in lineage commitment was also observed when 1nM FK506 was added 8h after the start of the culture. Delayed addition of 20microM U0126, an Mek (Erk kinase) inhibitor, also induced the switch. These results suggest that the intensity of calcineurin activity and the duration of both calcineurin and Erk pathway activation are crucial for thymocyte lineage commitment.

Animals↗
PubMed2003

Lineage choice and differentiation in mouse embryos and embryonic stem cells.

The use of embryonic stem (ES) cells for generating healthy tissues has the potential to revolutionize therapies for human disease or injury, for which there are currently no effective treatments. Strategies for manipulating stem cell differentiation should be based on knowledge of the mechanisms by which lineage decisions are made during early embryogenesis. Here, we review current research into the factors influencing lineage differentiation in the mouse embryo and the application of this knowledge to in vitro differentiation of ES cells. In the mouse embryo, specification of tissue lineages requires cell-cell interactions that are influenced by coordinated cell migration and cellular neighborhood mediated by the key WNT, FGF, and TGFbeta signaling pathways. Mimicking the cellular interactions of the embryo by providing appropriate signaling molecules in culture has enabled the differentiation of ES cells to be directed predominately toward particular lineages. Multistep strategies incorporating the provision of soluble factors known to influence lineage choices in the embryo, coculture with other cells or tissues, genetic modification, and selection for desirable cell types have allowed the production of ES cell derivatives that produce beneficial effects in animal models. Increasing the efficiency of this process can only result from a better understanding of the molecular control of cell lineage determination in the embryo.

Animals↗
PubMed2003

Comparison of the gene expression profiles of monocytic versus granulocytic lineages of HL-60 leukemia cell differentiation by DNA microarray analysis.

It is now recognized that precise patterns of differentially expressed genes ultimately direct a particular cell toward a given lineage. In this study, we compared the expression profiles of cancer-related genes by cDNA microarray analysis during the differentiation of human promyelocytic leukemia HL-60 cells into either monocytes or granulocytes. RNA was isolated at times 0, 6, 12, 24, 36, 48, and 72 h following stimulation of differentiation with all-trans retinoic acid (all-trans RA) or 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], and hybridized to the microarray gene chips containing 872 genes related to cell-cycles, oncogenes and leukemias. Several genes were commonly or differentially regulated during cell differentiation into either lineage, as demonstrated by both hierarchical and self-organizing map clustering analysis. At 72 h the expression levels of 45 genes were commonly up- or down-regulated at least a twofold in both lineages. Most importantly, 32 genes including alpha-L-fucosidase gene and adducin gamma subunit gene were up- or down-regulated only in all-trans RA-treated HL-60 cells, while 12 genes including interleukin 1beta and hypoxia-inducible factor 1alpha were up- or down-regulated only in 1,25-(OH)(2)D(3)-treated HL-60 cells. The expression of selected genes was confirmed by Northern blot analysis. As expected, some genes identified have not been examined during HL-60 cell differentiation into either lineage. The identification of genes associated with a specific differentiation lineage may give important insights into functional and phenotypic differences between two lineages of HL-60 cell differentiation.

Calcitriol↗
PubMed1997

Cell-lineage and clonal-contribution map of the trochophore larva of Patella vulgata (mollusca).

Molluscan development is characterised by its extremely regular cleavage pattern. In numerous molluscs the fate of various early-cleavage stage blastomeres has been determined and fate maps have been constructed. On the basis of similarities between these fate maps, a generalised molluscan cell-lineage map has been constructed. Recently, the validity of this map has been challenged. In this study, the cell-lineage of the first-, second-, and third-quartet micromeres and third-generation macromeres of the equally-cleaving gastropod mollusc Patella vulgata was studied by fluorescent cell-lineage tracer injection followed by epifluorescence microscopy and confocal laser scanning microscopy. For the first time, a complete cell-lineage map, in the form of a clonal-contribution map of the trochophore, has been constructed with the use of fluorescent cell-lineage tracers. This map both agrees and differs in a number of respects with the generalised cell-lineage map of molluscs. The most important deviation is that the micromere 2d, formerly referred to as the first somatoblast, is not the only cell that forms the foot and shell gland in Patella.

Animals↗
PubMed1996

Identification of the earliest B lineage stage in mouse bone marrow.

We have identified a very early stage of B lineage cells in the CD45R (B220)+CD24 (HSA) pre-pro-B fraction of mouse bone marrow delineated by expression of AA4.1, a molecule found on stem cells and early B lineage cells. These cells are B lineage precursors based on their capacity to generate B lineage cells rapidly in stromal-dependent culture and their expression of high levels of germline IgH transcripts in the absence of Rag-1/2. Half of these AA4.1+ precursors express low levels of CD4, characteristic of lymphoid progenitors, but few if any have up-regulated CD19, a molecule expressed very early in the B lineage. Furthermore, expression of genes encoding pre-B and B cell receptor components (mb-1, B29, and lambda 5) and transcription factors necessary for B lineage differentiation (BSAP, E12, E47, and Id) provide further support for designating these cells as the earliest B cell precursors.

Animals↗
PubMed2002

Divergent models of lymphoid lineage specification: do clonal assays provide all the answers?

Hematopoietic stem cells that drive blood development in mouse and man have been well characterized in recent years. In contrast, detailed analysis of the next stages of development, the progenitor cells that have begun to differentiate along specific hematopoietic lineages, is now only in its infancy. The process of myeloid differentiation has been relatively accessible to experimental manipulation due to the availability of culture systems able to support the progenitors for myeloid lineages, and the identification of cytokines capable of driving myeloid differentiation. Studies of early lymphoid differentiation, however, have lagged behind. In particular, the characterization of the first progenitors for the lymphoid lineages is far from complete, due mainly to inefficient assay systems for growing these cell lineages in vitro. Two laboratories have published conflicting data regarding the specification of lymphoid lineages in the mouse. Both groups of investigators utilize elegant clonal approaches to characterize progenitor cell subsets. While these experiments define lineage potential in the most rigorous manner possible, the divergent results suggest that clonal assays must be supplemented with more physiologic studies in order to define the actual differentiation pathways that function in vivo.

Animals↗
PubMed1999

Commitment to the B-lymphoid lineage depends on the transcription factor Pax5.

The Pax5 gene encoding the B-cell-specific activator protein (BSAP) is expressed within the haematopoietic system exclusively in the B-lymphoid lineage, where it is required in vivo for progression beyond the pro-B-cell stage. However, Pax5 is not essential for in vitro propagation of pro-B cells in the presence of interleukin-7 and stromal cells. Here we show that pro-B cells lacking Pax5 are also incapable of in vitro B-cell differentiation unless Pax5 expression is restored by retroviral transduction. Pax5-/- pro-B cells are not restricted in their lineage fate, as stimulation with appropriate cytokines induces them to differentiate into functional macrophages, osteoclasts, dendritic cells, granulocytes and natural killer cells. As expected for a clonogenic haematopoietic progenitor with lymphomyeloid developmental potential, the Pax5-/- pro-B cell expresses genes of different lineage-affiliated programmes, and restoration of Pax5 activity represses this lineage-promiscuous transcription. Pax5 therefore plays an essential role in B-lineage commitment by suppressing alternative lineage choices.

Animals↗
PubMed2005

The zinc finger transcription factor Th-POK regulates CD4 versus CD8 T-cell lineage commitment.

Development of immature T-cell precursors (thymocytes) to either the CD4 helper or CD8 killer T-cell lineages correlates precisely with their T-cell receptor specificity for major histocompatibility complex class II or class I molecules, respectively, indicating that the process is carefully regulated. Although intensively studied owing to its importance in determining the composition of the mature T-cell compartment and as a general model of binary lineage decisions, the underlying molecular pathways remain obscure. We have previously reported a spontaneous mouse mutant (HD (helper deficient) mice) in which lineage commitment is specifically perturbed without affecting positive selection. Here we show that a point mutation in the zinc finger transcription factor Th-POK (T-helper-inducing POZ/Krüppel-like factor) is responsible for redirection of class-II-restricted thymocytes to the CD8 lineage in HD mice. Furthermore, we demonstrate that constitutive expression of this factor during thymic development leads to redirection of class-I-restricted thymocytes to the CD4 lineage, indicating that Th-POK is a master regulator of lineage commitment.

Amino Acid Sequence↗
PubMed2006

BCR-ABL1 induces aberrant splicing of IKAROS and lineage infidelity in pre-B lymphoblastic leukemia cells.

Pre-B lymphoblastic leukemia cells carrying a BCR-ABL1 gene rearrangement exhibit an undifferentiated phenotype. Comparing the genome-wide gene expression profiles of normal B-cell subsets and BCR-ABL1+ pre-B lymphoblastic leukemia cells by SAGE, the leukemia cells show loss of B lymphoid identity and aberrant expression of myeloid lineage-specific molecules. Consistent with this, BCR-ABL1+ pre-B lymphoblastic leukemia cells exhibit defective expression of IKAROS, a transcription factor needed for early lymphoid lineage commitment. As shown by inducible expression of BCR-ABL1 in human and murine B-cell precursor cell lines, BCR-ABL1 induces the expression of a dominant-negative IKAROS splice variant, termed IK6. Comparing matched leukemia sample pairs from patients before and during therapy with the BCR-ABL1 kinase inhibitor STI571 (Imatinib), inhibition of BCR-ABL1 partially corrected aberrant expression of IK6 and lineage infidelity of the leukemia cells. To elucidate the contribution of IK6 to lineage infidelity in BCR-ABL1+ cell lines, IK6 expression was silenced by RNA interference. Upon inhibition of IK6, BCR-ABL1+ leukemia cells partially restored B lymphoid lineage commitment. Therefore, we propose that BCR-ABL1 induces aberrant splicing of IKAROS, which interferes with lineage identity and differentiation of pre-B lymphoblastic leukemia cells.

Alternative Splicing↗
PubMed2000

Cytokine requirement for the development of T-lymphoid lineage potential in clonal lymphohaematopoietic progenitors in vitro.

The early process of T-cell development prior to thymic colonization has been poorly investigated because of the lack of a sensitive assay. We have developed a two-step in vitro culture system by combining a clonal culture with a fetal thymus organ culture (FTOC) and analysed the early development of T cells from lymphohaematopoietic progenitors. Cells of immature colonies derived from bone marrow cells of 5-fluorouracil (5FU)-treated mice using various combinations of early acting cytokines were transferred into a FTOC. All the combinations of stem cell factor (SCF), interleukin (IL)-3 and IL-6 capable of inducing colony formation supported T-cell generation. IL-11 and the Flt3 ligand possessed T-lineage promotional effects similar to IL-6 and SCF respectively. However, there were some quantitative differences in the final T-cell yield among cytokine combinations. Thus, the commitment towards T lineage in lymphohaematopoietic progenitors may be an event determined intrinsically rather than induced by specific stimuli, but there may be a hierarchy between the activity of cytokines in further development. Furthermore, we examined the T-lineage potential of individual colonies derived from Lin(-)c-Kit(+)Sca-1(+) cells clone-sorted from post-5FU marrow cells. No colonies that contained only myelocytic progenitors showed T-lineage potential, but 23.3% of colonies with a haematopoietic multipotentiality did. Therefore, the divergence of the T lineage from other lineages such as myeloid potential may occur at an early stage of the hierarchy of haematopoiesis. The proposed method should prove valuable for exploring the molecular and cellular changes that occur during early T-cell development before thymic colonization.

Animals↗
PubMed2004

Lineage specificity of gene expression patterns.

The hematopoietic system offers many advantages as a model for understanding general aspects of lineage choice and specification. Using oligonucleotide microarrays, we compared gene expression patterns of multiple purified hematopoietic cell populations, including neutrophils, monocytes, macrophages, resting, centrocytic, and centroblastic B lymphocytes, dendritic cells, and hematopoietic stem cells. Some of these cells were studied under both resting and stimulated conditions. We studied the collective behavior of subsets of genes derived from the Biocarta database of functional pathways, hand-tuned groupings of genes into broad functional categories based on the Gene Ontology database, and the metabolic pathways in the Kyoto Encyclopedia of Genes and Genomes database. Principal component analysis revealed strikingly pervasive differences in relative levels of gene expression among cell lineages that involve most of the subsets examined. These results indicate that many processes in these cells behave differently in different lineages. Much of the variation among lineages was captured by the first few principal components. Principal components biplots were found to provide a convenient visual display of the contributions of the various genes within the subsets in lineage discrimination. Moreover, by applying tree-constructing methodologies borrowed from phylogenetics to the expression data from differentiated cells and stem cells, we reconstructed a tree of relationships that resembled the established hematopoietic program of lineage development. Thus, the mRNA expression data implicitly contained information about developmental relationships among cell types.

Cell Lineage↗
PubMed2006

Automated cell lineage tracing in Caenorhabditis elegans.

The invariant cell lineage and cell fate of Caenorhabditis elegans provide a unique opportunity to decode the molecular mechanisms of animal development. To exploit this opportunity, we have developed a system for automated cell lineage tracing during C. elegans embryogenesis, based on 3D, time-lapse imaging and automated image analysis. Using ubiquitously expressed histone-GFP fusion protein to label cells/nuclei and a confocal microscope, the imaging protocol captures embryogenesis at high spatial (31 planes at 1 microm apart) and temporal (every minute) resolution without apparent effects on development. A set of image analysis algorithms then automatically recognizes cells at each time point, tracks cell movements, divisions and deaths over time and assigns cell identities based on the canonical naming scheme. Starting from the four-cell stage (or earlier), our software, named starrynite, can trace the lineage up to the 350-cell stage in 25 min on a desktop computer. The few errors of automated lineaging can then be corrected in a few hours with a graphic interface that allows easy navigation of the images and the reported lineage tree. The system can be used to characterize lineage phenotypes of genes and/or extended to determine gene expression patterns in a living embryo at the single-cell level. We envision that this automation will make it practical to systematically decipher the developmental genes and pathways encoded in the genome of C. elegans.

Animals↗