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At least 19 recordsLinked to original sources

Myelomastocytic leukemia: myeloid neoplasm characterized by partial differentiation of mast cell-lineage cells.

A novel subtype of myeloid leukemia exhibiting a partial differentiation of mast cell-lineage cells is described. The disease is characterized by an increase in myeloblasts as well as an increase in immature (blast-like) metachromatic cells (>10% in bone marrow or blood smears). Metachromatic cells express KIT (CD117) and tryptase, but lack basophil-related antigens. In contrast to mast cell leukemia/systemic mastocytosis, metachromatic cells do not express CD2 or CD25, do not form multifocal dense aggregates in the bone marrow, and do not exhibit transforming mutations at codon 816 of c-kit. In the few patients recorded so far, a complex karyotype without recurring anomaly was found. The prognosis appears to be grave, although complete remission in response to chemotherapy has been described.

Cell Differentiation↗

Cell lineage, cell death, and the developmental origin of identified serotonin- and dopamine-containing neurons in the leech.

The nervous system of the glossiphoniid leech includes segmentally iterated neurons that contain serotonin (5-HT) and dopamine. These have been investigated in Helobdella triserialis, Theromyzon rude, and Haementeria ghilianii. Five types of 5-HT neurons are identified by immunocytochemistry in the abdominal ganglia of the ventral nerve cord: the bilaterally paired Retzius, anteromedial, ventrolateral and dorsolateral neurons, and the unpaired posteromedial (pm) neuron. Three types of bilaterally paired dopamine neurons are identified by glyoxylic acid-induced fluorescence in the segmental body wall: MD, LD1, and LD2. Each left or right half of the segmental complement of the leech nervous system is known to develop from 6 distinct ectodermal primary blast cells (ns, nf, o, p, qs, and qf). To identify the blast cells of origin of the 5-HT and dopamine neurons, fluorescent cell lineage tracers were injected into the various precursors of the blast cells in early (stage 6) embryos. The embryos were then raised until their 5-HT and dopamine neurons could be scored (stage 11) for the presence or absence of lineage tracer. We find that the Retzius, anteromedial, and posteromedial 5-HT neurons are derived from the ns blast cell, while the ventrolateral and dorsolateral 5-HT neurons are derived from the nf blast cell. The unpaired pm 5-HT neuron arises as one of a bilateral pair of neurons, of which one later dies. Whether the left or right pm neuron survives in any given ganglion is the consequence of some form of competitive interaction between cells derived from the left and right n primary blast cells, possibly between the left and right pm neurons themselves. We find that, of the dopamine neurons, the LD1 neuron is derived from the o blast cell, the LD2 neurons from the p blast cell, and the MD neuron from one of the 2 kinds of q blast cells. These results show that the 5-HT and dopamine neurons arise from 5 different primary blast cells in a highly determinate manner, and they support the view that cells of a similar phenotype need not be closely related in the developmental cell lineage tree.

Animals↗

Selective specification of CNS stem cells into oligodendroglial or neuronal cell lineage: cell culture and transplant studies.

Neural stem cells (NSCs) were isolated from embryonic day 16 Sprague-Dawley rats and cultured in a novel serum-free stem cell medium that selected for the growth of NSCs and against the growth of GFAP(+) cells (astrocytes). NSCs maintained in culture for extended periods of time retained immunoreactivity for both nestin and PSA-NCAM, two markers characteristic of the stem cell phenotype. Moreover, using an oligodendrocyte (OL) specification medium, NSCs differentiated into OL as evidenced by their morphology and expression of multiple oligodendrocyte/myelin-specific markers. In addition, NSCs are capable of acquiring a neuronal phenotype as evidenced by expressing neuronal markers, such as neurofilament (NF) and NeuN when cultured in a defined medium for neurons indicating that these cells are also a good source of neuroblasts, which could be used to replace neuronal populations in the brain. We also showed successful propagation and differentiation of NSCs into OL after cryostorage, allowing for the later use of stored NSCs. The long-term goal of culturing NSCs and committed oligodendrocyte progenitors (OLP) is to obtain homogeneous populations for transplantation with the goal of remyelinating the myelin-deficient CNS. Our preliminary experiments carried out on normal and myelin deficient rats demonstrate that these cells survive and migrate extensively in both types of hosts. NSCs grafted as such, as well as cells derived from NSCs exposed to selective specification before grafting, are able to differentiate within the host brain. As expected, NSCs are capable of giving rise to astrocytes in a medium favoring this phenotype.

Animals↗

Cell lineage, cell signaling and the control of plant morphogenesis.

It is clear that cell-cell signaling is critical for the development of both root and shoot structures. Recently, several of the key gene products required for intercellular signaling have been defined, and the developmental processes regulated by cell-cell interactions are beginning to be elucidated. Surprisingly, these results suggest that the mechanisms by which plant cells communicate with each other may be quite distinct from those used in animal systems.

Animals↗

Mutations that affect neural cell lineages and cell fates during the development of the nematode Caenorhabditis elegans.

We have described 19 genes that affect neural cell lineages and cell fates during the development of C. elegans. These genes differ markedly in the nature, breadth, and specificity of their effects. Their only obvious common characteristic is that they all lack specificity for the nervous system, affecting both neural and nonneural development. For some of these genes (lin-5, lin-6, unc-59, unc-85), this nonspecificity probably reflects a general utilization of their products in cellular replication. In contrast, most of these genes appear to be highly specific in their effects, but their specificity is not on the basis of cell type but rather on the basis of some particular aspect of development. Specifically, unc-83 and unc-84 mutations affect certain precursor cells that generate both neural and nonneural descendants; lin-22 and lin-26 mutants lead to the generation of supernumerary neural cells with a concomitant loss of nonneural cells; lin-4, lin-14, lin-28, and lin-29 mutants perturb global aspects of developmental timing, altering the time of appearance (or preventing the appearance) of both neural and nonneural cells; lin-1, lin-8, lin-9, and lin-15 mutations affect the cell lineages of certain nonneuron -producing ectoblasts in hermaphrodites and of homologous neuron-producing ectoblasts in males; lin-12 mutations affect many sets of nonidentical homologs (cells of similar lineage history that express different fates), only some of which are neural; ced-3 mutations prevent all programmed cell deaths, again only some of which are neural. Of these 19 genes, only unc-86 is specific for neural as opposed to nonneural cell lineages. However, some unc-86 mutants are abnormal in chromosome segregation at meiosis, indicating that this gene also may affect nonneural aspects of development. One implication of these observations is that genes (and molecules) involved in neural development are likely to function in nonneural development as well. The genes lin-22, lin-12, unc-86, and ced-3 may play decision-making roles during C. elegans neurogenesis, as mutations in each of these genes cause specific transformations in the fates of particular cells. These genes and others like them may act within a hierarchy to effect decisions at different levels within cell lineages. For example, lin-22 animals display transformations affecting entire postembryonic cell lineages, unc-86 animals are altered at an intermediate level of certain cell lineages, and ced-3 animals are affected only in the ultimate fates of cells produced by terminal cell divisions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Neurogenesis of the peripheral nervous system in Drosophila embryos: DNA replication patterns and cell lineages.

Cell lineages that give rise to the PNS were studied using the thymidine analog 5-bromo-2'-deoxyuridine (BrdU) to visualized DNA replication immunocytochemically. The precursors of the PNS in the body segments of Drosophila embryos replicate their DNA in a spatially and temporally stereotyped pattern. The sequence of DNA replication within developing sensory organs suggests particular lineage relationships of the cells that constitute a sensory organ, i.e., neuron and associated support cells. In embryos that are mutant for the achaete-scute complex or daughterless, in which most or all of the PNS is missing, no BrdU-labeled cells were found in the appropriate regions, suggesting that these PNS precursors either do not form or fail to replicate. Thus, the BrdU technique allows determination as to whether a mutation affects the PNS precursors or terminal differentiation.

Animals↗

Neurobiological aspects of glial cells: astrocyte subtypes and the 0-2A glial cell lineage.

Cell culture studies have shown the existence, in the rat CNS, of two populations of astrocytes, generally named type-1 and type-2 astrocytes, differing in a number of morphological, antigenic and functional features, and belonging to two different cell lineages. Type-2 astrocytes seem to derive from a bipotential glial progenitor cell (0-2A progenitor) which gives rise also to oligodendrocytes. Several epigenetic factors influence the proliferation and the differentiation destiny of 0-2A progenitors. Among such factors, heterotypic and homotypic glial cell interactions appear to be particularly important. Interaction with factors present on the surface of type-1 astrocytes or in their extracellular matrix leads to an increased proliferation of 0-2A progenitors and facilitates their oligodendroglial differentiation, while homotypic interactions among the progenitors induce them to differentiate into oligodendrocytes through the secretion of autocrine non mitogenic factors.

Animals↗

Cell lineage and cell states in the Drosophila embryo.

Much of this essay is a cautionary tale about the inherent difficulty of building theories to explain pattern formation in embryos. In particular, I discuss the relationship between cell state and cell lineage. The idea that embryonic cells can occupy discrete genetic states is an old one but, because of the mass of new information from Drosophila developmental genetics, it has been given new life. I propose an operational definition of a cell state and argue that a true cell state should be propagated faithfully through cell lineage for at least some divisions. The genes involved should have a controlling role and the borders between populations of cells in two different states should be so sharp that cells fall clearly into one state or another.

Animals↗

Cell lineage and cell migration in the neural crest.

The neural crest is a transient embryonic structure whose cells migrate extensively before giving rise to a variety of differentiated cell types. Both intrinsic cell lineage information and environmental cues are thought to play a role in determining the fate of these cells. Early in development, these cells can be divided into distinct populations based on their axial level of origin. Cranial neural crest cells differentiate into facial cartilage and cranial ganglia, whereas vagal crest cells give rise to the enteric ganglia. Trunk neural crest cells normally give rise to melanocytes, neurons, and glia of the peripheral nervous system and chromaffin cells of the adrenal medulla. Cell lineage studies of premigratory trunk neural crest cells using single cell injection of a vital dye have shown that single cells can give rise to a number of differentiated cell types. A host of extracellular matrix (ECM) molecules have been tested for their ability to support neural crest cell migration in vitro and in vivo. In general, the large glycoproteins (i.e., fibronectin and laminin) can support migration, whereas proteoglycans seem to modulate neural crest cell migration on other ECM molecules. However, no single molecule has been identified as the sole regulator of the complex pattern of neural crest cell migration.

Cell Adhesion↗

Cell lineage and cell fate in crustacean embryos--a comparative approach.

Malacostracan crustaceans undergo a complex and stereotyped cleavage pattern during formation of and segmentation in their post-naupliar germ band. This pattern has been studied in several malacostracan representatives with respect to morphogenesis and expression of the engrailed gene. Although this cell lineage pattern is specific and invariant in each species, comparative analyses reveal subtle differences between different parts of individual germ bands and between germ bands of different species. We conclude that despite the elaborate cleavage pattern, cell fate specification is not closely linked to cell lineage. Furthermore, some aspects of the evolutionary alterations of germ band formation and segmentation in annelids and arthropods are discussed.

Animals↗

Cell lineage, cell-cell interaction, and segment formation in the ectoderm of a glossiphoniid leech embryo.

Cell division patterns and cell-cell interactions in the germinal bands of the glossiphoniid leech Helobdella triserialis were studied with the aid of a cell lineage tracer dye. Each germinal band of the Helobdella embryo consists of five columns, or bandlets, of primary blast cells, designated as the mesodermal m bandlet and ectodermal n, o, p, and q bandlets. Primary blast cells of each ectodermal bandlet appear to undergo stereotyped, lineage-specific cell divisions. The metameric segmentation pattern of the leech thus appears to arise through a series of segmentally iterated, stereotyped cell divisions of serially homologous primary blast cell clones. Cell-cell interactions were studied by means of cell ablations. With one exception, blast cells underwent their stereotyped divisions without regard to the presence or absence of their normal neighbors. In the one exceptional case, o blast cells underwent divisions normally characteristic of p blast cells when their normal neighboring p bandlet was deleted. However, both o and p blast cells underwent their normal stereotyped divisions when their neighboring m, n, and q bandlets were deleted. It is proposed that the differential choice of pathway by the o and p blast cells depends upon their relative position with respect to each other and to a polarity cue external to the germinal band.

Animals↗

The development of T and non-T cell lineages from CD34+ human thymic precursors can be traced by the differential expression of CD44.

In addition to T-lineage cells, a small proportion of hematopoietic non-T cells are present in the human postnatal thymus. However, the origin of this minor non-T cell thymic compartment is presently unknown. In this study we have analyzed the developmental potential of the earliest human intrathymic precursors, characterized as CD34+ cells expressing intermediate levels of CD44. We show that these CD34+CD44int thymocytes cultured with interleukin 7 were able to develop simultaneously into both T- and non-T (monocytes and dendritic cells) -lineage cells. Both developmental pathways progress through a CD1+CD4+ intermediate stage, currently believed to be the immediate precursor of double positive thymocytes. However, separate progenitors for either T or non-T cells could be characterized within CD1+CD4+ thymocytes by their opposite expression of CD44. Downregulated levels of CD44 identified CD1+CD4+ T-lineage precursors, whereas CD44 upregulation occurred on CD1+CD4+ intermediates that later differentiated into non-T cells. Therefore, commitment of human early intrathymic precursors to either T or non-T cell lineages can be traced by the differential expression of the CD44 receptor.

Antigens↗

How far does cell lineage influence cell fate specification in crustacean embryos?

In crustaceans, invariant cell lineages have been shown to occur (i) in early cleavages of several taxa and (ii) in the course of formation and differentiation of the post-naupliar germ bands in malacostracans. Work on early cleavages is still in its infancy. In contrast, the generation and proliferation of mesoteloblasts and ectoteloblasts and the subsequent proliferation and differentiation of bandlet cells have been studied in members of several subgroups of Malacostraca. Similarities and differences have been determined in order to interpret the interdependencies of the steps in the differentiation process. Some of these steps are highly conserved, as in the case of the generation of four pairs of mesoteloblasts, others are prone to phylogenetic change, as in the case of the primary ring of 19 ectoteloblasts which has been altered at least twice in evolution. A stereotyped cleavage pattern in the germ band has been shown to be independent of the origin of the precursor cells. The question whether neuroblasts in crustaceans and insects are homologous or are the result of convergent evolution is still open. However, the homology of early differentiating neurons in crustaceans and insects seems to be well established. In addition, similarities in the expression patterns of the engrailed gene are likely to be homologous and point to a close relationship between these two groups.

Journal Article↗

The unc-86 gene product couples cell lineage and cell identity in C. elegans.

The C. elegans gene unc-86 is required in several distinct neuroblast lineages for daughter cells to become different from their mothers, and is also required for the specification of particular neural identities. Consistent with the fact that unc-86 encodes a POU domain protein, we find that the unc-86 protein is localized to the nucleus. In the affected lineages, unc-86 protein appears within a few minutes after cell division in the nuclei of those daughter cells that are transformed by unc-86 mutations. Thus, expression of unc-86 protein is dependent on cell lineage. unc-86 protein is not asymmetrically segregated at further divisions. unc-86 protein also appears shortly after cell division in the nuclei of particular identified differentiating neurons; at least some of these neurons are nonfunctional in unc-86 mutants.

Animals↗

Bone marrow and thymus expression of interferon-gamma results in severe B-cell lineage reduction, T-cell lineage alterations, and hematopoietic progenitor deficiencies.

Interferon-gamma (IFN-gamma) is an immunoregulatory lymphokine that is primarily produced by T cells and natural killer cells. It has effects on T-cell, B-cell, and macrophage differentiation and maturation. We have developed transgenic mice that express elevated levels of IFN-gamma mRNA and protein by inserting multiple copies of murine IFN-gamma genomic DNA containing an Ig lambda-chain enhancer in the first intron. The founder line carrying eight copies of this transgene has eightfold to 15-fold more IFN-gamma-producing cells in the bone marrow and spleen than do nontransgenic littermates. Transgenic mice show a pronounced reduction in B-lineage cells in the bone marrow, spleen, and lymph nodes. In addition, single positive (CD4+,CD8- and CD4-,CD8+) thymocyte numbers are increased twofold, yet the number of splenic T cells is reduced by 50%. There is also a twofold to threefold decrease in the frequency and total number of myeloid progenitors in the bone marrow. Granulomatous lesions and residual degenerating cartilaginous masses are also present in the bones of these mice. Overall, our data show that the abnormal expression of IFN-gamma in these transgenic mice results in multiple alterations in the immune system. These animals provide an important model to examine the role of IFN-gamma expression on lymphoid and myeloid differentiation and function.

Animals↗

Cutting edge: Ig heavy chain 3' HS1-4 directs correct spatial position-independent expression of a linked transgene to B lineage cells.

The Ig H chain locus is regulated by a set of cis-acting elements. Hypersensitive sites (HS) located 3' of the IgH, HS1-4, has been suggested to act as a locus control region (LCR) in cell lines. To assess the proposed role of HS1-4 acting as an LCR, we generated transgenic mice harboring a VH promoter-beta-globin reporter gene linked to the Ig H chain HS1-4 3'regulatory sequences. Transgene expression is strictly confined to B lymphocytes, with no detectable expression outside the B cell lineage in all transgenic founder lines. Furthermore, reporter gene activity is integration independent but not copy number dependent. Thus, additional sequences are required to allow the HS1-4 regulatory region to act as a classical LCR in mice. Our data are discussed in the context of tissue-specific gene expression in B lineage cells.

3' Untranslated Regions↗

Surface antigens of murine hemopoietic stem cells. IV. Characteristics of antisera exhibiting cell-lineage specificity, and differentiating ability of stem cells surviving treatment with antisera against cell-lineage antigens.

Hemopoietic stem cells express cell-lineage antigens in common with platelets, thymocytes and macrophages. Further evidence for the cell-lineage antigen model is presented. Erythrocyte-absorbed antiserum against purified mouse neutrophils cross-reacts with the hemopoietic stem cell in a lineage-specific manner. Thus, most of the anti-stem cell activity is absorbed out with neutrophils but not by other non-granulocytic hemopoietic cells. Of the four antisera tested for anti-stem cell activity, antiplatelet serum showed the highest degree of cell-lineage specificity (96% of the anti-stem cell activity satisfied cell-lineage criteria). To test predictions of the cell-lineage model of hemopoietic cell differentiation concerning the differentiating potential of stem cells selected for low concentration of cell-lineage antigen, bone marrow cells were treated with antiplatelet serum at a predetermined concentration required to produce 75-85% loss of spleen colonies. Stem cells surviving this treatment showed normal ability to form megakaryocytes and platelets. The results are consistent with postulates of the cell-lineage model.

Animals↗