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Precursor Cells (precursor + cell)
Kinds of Precursor Cells Terms modified by Precursor Cells Selected AbstractsAdult neurogenesis in the crayfish brain: Proliferation, migration, and possible origin of precursor cellsDEVELOPMENTAL NEUROBIOLOGY, Issue 7 2009Yi Zhang Abstract The birth of new neurons and their incorporation into functional circuits in the adult brain is a characteristic of many vertebrate and invertebrate organisms, including decapod crustaceans. Precursor cells maintaining life-long proliferation in the brains of crayfish (Procambarus clarkii, Cherax destructor) and clawed lobsters (Homarus americanus) reside within a specialized niche on the ventral surface of the brain; their daughters migrate to two proliferation zones along a stream formed by processes of the niche precursors. Here they divide again, finally producing interneurons in the olfactory pathway. The present studies in P. clarkii explore (1) differential proliferative activity among the niche precursor cells with growth and aging, (2) morphological characteristics of cells in the niche and migratory streams, and (3) aspects of the cell cycle in this lineage. Morphologically symmetrical divisions of neuronal precursor cells were observed in the niche near where the migratory streams emerge, as well as in the streams and proliferation zones. The nuclei of migrating cells elongate and undergo shape changes consistent with nucleokinetic movement. LIS1, a highly conserved dynein-binding protein, is expressed in cells in the migratory stream and neurogenic niche, implicating this protein in the translocation of crustacean brain neuronal precursor cells. Symmetrical divisions of the niche precursors and migration of both daughters raised the question of how the niche precursor pool is replenished. We present here preliminary evidence for an association between vascular cells and the niche precursors, which may relate to the life-long growth and maintenance of the crustacean neurogenic niche. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009 [source] Neural precursor cells from a fatal human motoneuron disease differentiate despite aberrant gene expressionDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2007Niklas Pakkasjärvi Abstract Precursor cells of the human central nervous system can be cultured in vitro to reveal pathogenesis of diseases or developmental disorders. Here, we have studied the biology of neural precursor cells (NPCs) from patients of lethal congenital contracture syndrome (LCCS), a severe motoneuron disease leading to prenatal death before the 32nd gestational week. LCCS fetuses are immobile because of a motoneuron defect, seen as degeneration of the anterior horn and descending tracts of the developing spinal cord. The genetic defect for the syndrome is unknown. We show that NPCs isolated postmortem from LCCS fetuses grow and are maintained in culture, but display increased cell cycle activity. Global transcript analysis of undifferentiated LCCS precursor cells present with changes in EGF-related signaling when compared with healthy age-matched human controls. Further, we show that LCCS-derived NPCs differentiate into cells of neuronal and glial lineage and that the initial differentiation is not accompanied by overt apoptosis. Cells expressing markers Islet-1 and Hb9 are also generated from the LCCS NPCs, suggesting that the pathogenic mechanism of LCCS does not directly affect the differentiation capacity or survival of the cells, but the absence of motoneurons in LCCS may be caused by a noncell autonomous mechanism. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007 [source] Human thymic epithelial cells maintain long-term survival of clonogenic myeloid and erythroid progenitor cells in vitroBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2000Katsuto Takenaka Precursor cells that migrate into the thymus are still multipotent. Therefore, thymic epithelial cells (TECs) may provide microenvironments not only for T-cell development, but also for maintenance of multipotent precursor cells until they undergo T-cell commitment. In the present study, we performed long-term cultures of CD34+ bone-marrow (BM) cells on TEC lines that were derived from cortical epithelial cells of post-natal thymus, to investigate whether human TECs could maintain long-term non-lymphoid haematopoiesis. Haematopoietic cells maintained in direct contact with established TEC lines were able to generate clonogenic progeny to both myeloid and erythroid cells for periods in excess of 5 weeks. Their abilities to support colony-forming units of granulocytes,macrophages (CFU-GM) and burst-forming units of erythroids (BFU-E) were almost equal to those of BM stromal cells. We observed similar results by using cloned TEC lines derived by limiting dilution, as well as those by using parental TEC lines. Colony-forming activities were maintained even when haematopoietic progenitor cells were physically separated from TEC lines and cultured on microporous membrane. These observations indicate that haematopoiesis maintained in TEC-contact long-term cultures may depend on soluble factors produced by TEC lines. Our results suggest that thymic cortical epithelial cells have the ability to support not only the differentiation of haematopoietic cells, but also long-term survival of clonogenic myeloid/erythroid progenitor cells. [source] Astrocytes promote neurogenesis from oligodendrocyte precursor cellsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2006P. M. Gaughwin Abstract The oligodendrocyte precursor cell (OPC) has until recently been regarded as a lineage-restricted precursor cell. Considerable interest has been generated by reports suggesting that OPCs may possess a wider differentiation potential than previously assumed and thus be considered a multipotential stem cell. This study examined the neuronal differentiation potential of rat, postnatal cortical OPCs in response to extracellular cues in vitro and in vivo. OPCs did not exhibit intrinsic neuronal potential and were restricted to oligodendrocyte lineage potential following treatment with the neural precursor mitogen fibroblast growth factor 2. In contrast, a postnatal hippocampal astrocyte-derived signal(s) is sufficient to induce functional neuronal differentiation of cortical OPCs in vitro in population and single cell studies. Co-treatment with Noggin, a bone morphogenetic protein antagonist, did not attenuate neuronal differentiation. Following transplantation to the adult rat hippocampus, cortical OPCs expressed doublecortin, a neuroblast-associated marker. The present findings show that hippocampal, astrocyte-derived signals can induce the neuronal differentiation of OPCs through a Noggin-independent mechanism. [source] Mixed (composite) glandular-endocrine cell carcinoma of the gallbladderHPB, Issue 1 2001N Yannakou Background A mixed pattern of glandular and neuroendocrine elements is rare in tumours at any site within the gastrointestinal tract but particularly so in the gallbladder. Case outline A 72-year-old woman presented with abdominal pain and jaundice and was found to have a large mass in the fundus of the gallbladder. The mass was radically excised to include a wedge of liver and the hepatoduodenal lymph nodes. Histopathological examination of the resected gallbladder showed an invasive tumour composed of both adenocarcinoma and endocrine cell carcinoma, with apparent transitions between them. The patient received no further treatment and died two months later. Discussion There are 14 previous case reports of mixed adeno/endocrine carcinoma of the gallbladder. Histochemical similarities between the two neoplastic components of the present tumour would support their origin from a common precursor cell, but the alternative hypothesis of coincidental neoplastic change in two different cell types cannot be excluded. [source] Adult-derived stem cells and their potential for use in tissue repair and molecular medicineJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 3 2005Henry E. Young Abstract This report reviews three categories of precursor cells present within adults. The first category of precursor cell, the epiblast-like stem cell, has the potential of forming cells from all three embryonic germ layer lineages, e.g., ectoderm, mesoderm, and endoderm. The second category of precursor cell, the germ layer lineage stem cell, consists of three separate cells. Each of the three cells is committed to form cells limited to a specific embryonic germ layer lineage. Thus the second category consists of germ layer lineage ectodermal stem cells, germ layer lineage mesodermal stem cells, and germ layer lineage endodermal stem cells. The third category of precursor cells, progenitor cells, contains a multitude of cells. These cells are committed to form specific cell and tissue types and are the immediate precursors to the differentiated cells and tissues of the adult. The three categories of precursor cells can be readily isolated from adult tissues. They can be distinguished from each other based on their size, growth in cell culture, expressed genes, cell surface markers, and potential for differentiation. This report also discusses new findings. These findings include the karyotypic analysis of germ layer lineage stem cells; the appearance of dopaminergic neurons after implantation of naive adult pluripotent stem cells into a 6-hydroxydopamine-lesioned Parkinson's model; and the use of adult stem cells as transport mechanisms for exogenous genetic material. We conclude by discussing the potential roles of adult-derived precursor cells as building blocks for tissue repair and as delivery vehicles for molecular medicine. [source] Muscle precursor cells isolated from aged rats exhibit an increased tumor necrosis factor-, responseAGING CELL, Issue 1 2009Simon J. Lees Summary Improving muscle precursor cell (MPC, muscle-specific stem cells) function during aging has been implicated as a key therapeutic target for improving age-related skeletal muscle loss. MPC dysfunction during aging can be attributed to both the aging MPC population and the changing environment in skeletal muscle. Previous reports have identified elevated levels of tumor necrosis factor-, (TNF-,) in aging, both circulating and locally in skeletal muscle. The purpose of the present study was to determine if age-related differences exist between TNF-,-induced nuclear factor-kappa B (NF-,B) activation and expression of apoptotic gene targets. MPCs isolated from 32-month-old animals exhibited an increased NF-,B activation in response to 1, 5, and 20 ng mL,1 TNF-,, compared to MPCs isolated from 3-month-old animals. No age differences were observed in the rapid canonical signaling events leading to NF-,B activation or in the increase in mRNA levels for TNF receptor 1, TNF receptor 2, TNF receptor-associated factor 2 (TRAF2), or Fas (CD95) observed after 2 h of TNF-, stimulation. Interestingly, mRNA levels for TRAF2 and the cell death-inducing receptor, Fas (CD95), were persistently upregulated in response to 24 h TNF-, treatment in MPCs isolated from 32-month-old animals, compared to 3-month-old animals. Our data indicate that age-related differences may exist in the regulatory mechanisms responsible for NF-,B inactivation, which may have an effect on TNF-,-induced apoptotic signaling. These findings improve our understanding of the interaction between aged MPCs and the changing environment associated with age, which is critical for the development of potential clinical interventions aimed at improving MPC function with age. [source] pH is an intracellular effector controlling differentiation of oligodendrocyte precursors in culture via activation of the ERK1/2 pathwayJOURNAL OF NEUROSCIENCE RESEARCH, Issue 7 2006Frédéric Bernard Abstract We reported previously that onset of oligodendrocyte precursor cell (OPC) differentiation is accompanied by an increase in intracellular pH (pHi). We show that OPC differentiation is dependent primarily on a permissive pHi value. The highest differentiation levels were observed for pHi values around 7.15 and inhibition of differentiation was observed at slightly more acidic or alkaline values. Clamping the pHi of OPCs at 7.15 caused a transient activation of ERK1/2 that was not observed at more acidic or alkaline values. Furthermore, inhibition of ERK activation with the UO126 compound totally prevented OPC differentiation in response to pHi shift. These results indicate that pHi, acting through the ERK1/2 pathway, is a key determinant for oligodendrocyte differentiation. We also show that this pHi pathway is involved in the process of retinoic acid-induced OPC differentiation. © 2006 Wiley-Liss, Inc. [source] Alcohol Exposure Impairs Myeloid Dendritic Cell Function in Rhesus MacaquesALCOHOLISM, Issue 9 2009Robert W. Siggins Background:, Alcohol intoxication suppresses both the innate and adaptive immunities. Dendritic cells (DCs) are the major cell type bridging the innate and acquired immune responses. At the present time, the effects of alcohol on DC development in hematopoietic tissues and the functional activities of DCs are incompletely elucidated. This study investigated the impact of chronic alcohol exposure on the alteration of hematopoietic precursor cell and DC populations in the bone marrow and peripheral blood of rhesus macaques. Methods:, Rhesus macaques were administered alcohol or isocaloric sucrose daily for a period of 3 months through surgically implanted gastric catheters. Peripheral blood mononuclear cells (PBMCs) and bone marrow cells (BMCs) were isolated for flow cytometric analysis after 3 months. Monocytes were cultured with human IL-4 (10 ng/ml) and GM-CSF (50 ng/ml) in the absence and presence of alcohol (50 mM). On day 6 of the culture, a cocktail of stimulants including IL-1, (18 ng), IL-6 (1800 U), TNF-, (18 ng), and PGE2 (1.8 ,g) were added to the designated wells for transformation of immature dendritic cells (iDCs) to mature myeloid DCs. The cells were analyzed on day 8 by flow cytometry for expression of DC costimulatory molecule expression. Results:, EtOH-treated animals had significantly lower numbers of myeloid DCs (lineage-HLA-DR+CD11c+CD123,) in both the PBMCs and BMCs compared to controls (5,654 ± 1,273/106 vs. 2,353 ± 660/106 PBMCs and 503 ± 34 vs. 195 ± 44/106 BMCs). Under culture conditions, the number of lineage-HLA-DR+CD83+ cells was low in control wells (0.38 ± 0.08%). Alcohol inhibited the increase in the number of lineage-HLA-DR+CD83+ cells in iDC wells (2.30 ± 0.79% vs. 5.73 ± 1.40%). Alcohol also inhibited the increase in the number of lineage-HLA-DR+CD83+ cells in mature DC wells (1.23 ± 0.15% vs. 4.13 ± 0.62%). Conclusions:, Chronic EtOH decreases the bone marrow and circulating pools of myeloid DCs. Additionally, EtOH suppresses costimulatory molecule CD83 expression during DC transformation, which may attenuate the ability of DCs to initiate T-cell expansion. [source] Preclinical evaluation of carcinoembryonic cell adhesion molecule (CEACAM) 6 as potential therapy target for pancreatic adenocarcinoma,THE JOURNAL OF PATHOLOGY, Issue 3 2009Laura A Strickland Abstract Despite the availability of new targeted therapies, ductal pancreatic adenocarcinoma continues to carry a poor prognosis. Carcinoembryonic antigen-related cell adhesion molecule (CEACAM)6 has been reported as a potential biomarker and therapy target for this malignancy. We have evaluated CEACAM6 as a potential therapy target, using an antibody,drug conjugate (ADC). Expression of CEACAM6 in pancreatic adenocarcinomas was determined using immunohistochemistry on tissue microarrays. The expression pattern in granulocytes and granulocytic precursors was measured by flow cytometry. Murine xenograft and non-human primate models served to evaluate efficacy and safety, respectively. Robust expression of CEACAM6 was found in > 90% of invasive pancreatic adenocarcinomas as well as in intraepithelial neoplastic lesions. In the granulocytic lineage, CEACAM6 was expressed at all stages of granulocytic maturation except for the early lineage-committed precursor cell. The anti-CEACAM6 ADC showed efficacy against established CEACAM6-expressing tumours. In non-human primates, antigen-dependent toxicity of the ADC consisted of dose-dependent and reversible depletion of granulocytes and their precursors. This was associated with preferential and rapid localization of the antibody in bone marrow, as determined by sequential in vivo PET imaging of the radiolabelled anti-CEACAM6. Localization of the radiolabelled tracer could be attenuated by predosing with unlabelled antibody confirming specific accumulation in this compartment. Based on the expression pattern in normal and malignant pancreatic tissues, efficacy against established tumours and limited and reversible bone marrow toxicity, we propose that CEACAM6 should be considered for an ADC-based therapy approach against pancreatic adenocarcinomas and possibly other CEACAM6-positive neoplasms. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] A Synthetic Mechano Growth Factor E Peptide Enhances Myogenic Precursor Cell Transplantation SuccessAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2007P. Mills Myogenic precursor cell (MPC) transplantation is a good strategy to introduce dystrophin expression in muscles of Duchenne muscular dystrophy (DMD) patients. Insulin-like growth factor (IGF-1) promotes MPC activities, such as survival, proliferation, migration and differentiation, which could enhance the success of their transplantation. Alternative splicing of the IGF-1 mRNA produces different muscle isoforms. The mechano growth factor (MGF) is an isoform, especially expressed after a mechanical stress. A 24 amino acids peptide corresponding to the C-terminal part of the MGF E domain (MGF-Ct24E peptide) was synthesized. This peptide had been shown to enhance the proliferation and delay the terminal differentiation of C2C12 myoblasts. The present study showed that the MGF-Ct24E peptide improved human MPC transplantation by modulating their proliferation and differentiation. Indeed, intramuscular or systemic delivery of this synthetic peptide significantly promoted engraftment of human MPCs in mice. In vitro experiments demonstrated that the MGF-Ct24E peptide enhanced MPC proliferation by a different mechanism than the binding to the IGF-1 receptor. Moreover, MGF-Ct24E peptide delayed human MPC differentiation while having no outcome on survival. Those combined effects are probably responsible for the enhanced transplantation success. Thus, the MGF-Ct24E peptide is an interesting agent to increase MPC transplantation success in DMD patients. [source] Gastrointestinal stromal tumors (GISTs): a reviewAPMIS, Issue 2 2009SONJA E. STEIGEN Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms in the gastrointestinal tract, which, over the last 10 years, have emerged from a poorly understood neoplasm to a well-defined tumor entity exhibiting particular molecular abnormalities and for which promising novel treatment modalities have been developed. GISTs probably arise from the precursor cell of the interstitial cell of Cajal, express KIT tyrosine kinase in most of the cases and harbor mutations of importance for individualized treatment. The molecular targets for therapeutic interventions are not only of importance for the treatment of GIST patients but also useful for in the development of novel drug modalities and new strategies in basic cancer therapy. [source] Role of interleukin-15 in the development of mouse olfactory nerveCONGENITAL ANOMALIES, Issue 4 2009Tsuyoshi Umehara ABSTRACT Interleukin (IL)-15 interacts with components of the IL-2 receptor (R) and exhibits T cell-stimulating activity similar to that of IL-2. In addition, IL-15 is widely expressed in many cell types and tissues, including the central nervous system. We provide evidence of a novel role of IL-15 in olfactory neurogenesis. Both IL-15 and IL-15R, were expressed in neuronal precursor cells of the developing olfactory epithelium in mice. Adult IL-15R, knockout mice had fewer mature olfactory neurons and proliferating cells than wild-type. Our results suggest that IL-15 plays an important role in regulating cell proliferation in olfactory neurogenesis. [source] Epigenetic control of skeletal muscle fibre typeACTA PHYSIOLOGICA, Issue 4 2010K. Baar Abstract Adult muscle is extremely plastic. However, the muscle precursor cells associated with those fibres show stable and heritable differences in gene expression indicative of epigenetic imprinting. Epigenetic processes in the development of skeletal muscle have been appreciated for over a decade; however, there are a paucity of studies looking at whether epigenetics determines the phenotype of adult and/or ageing skeletal muscle. This review presents the evidence that epigenetics plays a role in determining adult muscle function and a series of unanswered questions that would greatly increase our understanding of how epigenetics works in adult muscle. With the increased interest in epigenetics, over the next few years this field will begin to unfold in unimaginable directions. [source] Flow cytometric differential of leukocyte populations in normal bone marrow: Influence of peripheral blood contamination1,CYTOMETRY, Issue 1 2009R. A. Brooimans Abstract Background: Availability of immunophenotypic reference values for the various leukocyte populations distributed in bone marrow may be helpful to recognize abnormal bone marrow development and, therefore, useful as first screening of individuals with suspected hematological malignancies or other hematopoietic disorders. Methods: A single tube four-color staining panel (CD66abce/CD14/CD45/CD34) together with a predefined gating strategy was utilized to immunologically differentiate the distribution of the major leukocyte populations in bone marrow aspirates of healthy donors. The sample-blood erythrocyte ratio was applied to assess the amount of blood contamination of marrow and account for this in the marrow value estimates. Results: The frequency of the major leukocyte populations in bone marrow of 134 normal donors were for granulocytes: mean, 69.4%; SD, 10.3%; monocytes: mean, 4.7%; SD, 2.3%; lymphocytes: mean, 18.3%; SD, 8.7%. The frequency of the immature cell population that included precursor cells of each of the cell lineages among other cell types were mean 5.0%; SD 2.2%. The mean percentage of CD34 positive cells was 1.5%; SD 0.7%. Our results showed further that the frequency of cell populations, of which the presence is restricted to the bone marrow (e.g., CD34+ progenitor cells), is influenced by the degree of peripheral blood admixture. Between the total immature cells and purity of the bone marrow, there was a significant positive correlation demonstrated, whereas a negative correlation was found between the percentages of both lymphocytes as monocytes and the purity of the bone marrow. Conclusions: With a single tube-staining panel, we obtained reference values for flow cytometric assessment of all relevant leukocyte populations present in bone marrow that can be used as a frame of reference for better recognition of individuals with abnormal hematopoiesis. In addition, we have demonstrated the influence of the degree of peripheral blood admixture in the bone marrow aspirates on those reference values. © 2008 Clinical Cytometry Society [source] Periostin promotes a fibroblastic lineage pathway in atrioventricular valve progenitor cellsDEVELOPMENTAL DYNAMICS, Issue 5 2009Russell A. Norris Abstract Differentiation of prevalvular mesenchyme into valve fibroblasts is an integral step towards the development of functionally mature cardiac valves. Although clinically relevant, little is known regarding the molecular and cellular mechanisms by which this process proceeds. Genes that are regulated in a spatio-temporal pattern during valve remodeling are candidates for affecting this differentiation process. Based on its expression pattern, we have focused our studies on the role of the matricellular gene, periostin, in regulating the differentiation of cushion mesenchymal cells into valve fibroblasts. Herein, we demonstrate that periostin expression is coincident with and regulates type I collagen protein production, a major component of mature valve tissue. Adenoviral-mediated knock-down of periostin in atrioventricular mesenchyme resulted in a decrease in collagen I protein expression and aberrant induction of myocyte markers indicating an alteration in AV mesenchyme differentiation. In vitro analyses using a novel "cardiotube" assay further demonstrated that expression of periostin regulates lineage commitment of valve precursor cells. In these cells, expression of periostin and collagen I are regulated, in part, by TGF,-3. We further demonstrate that TGF,-3, through a periostin/collagen pathway, enhances the viscoelastic properties of AV cushion tissue surface tension and plays a crucial role in regulating valve remodeling. Thus, data presented here demonstrate that periostin, a TGF,-3 responsive gene, functions as a crucial mediator of chick AV valve maturation via promoting mesenchymal-to-fibroblast differentiation while blocking differentiation of alternative cell types (myocytes). Developmental Dynamics 238:1052,1063, 2009. © 2009 Wiley-Liss, Inc. [source] Nestin expression in pancreatic endocrine and exocrine cells of mice lacking glucagon signalingDEVELOPMENTAL DYNAMICS, Issue 4 2007Mamdouh H. Kedees Abstract Nestin, a marker of neural stem cells, is also expressed by cells located in the epithelium of the pancreatic primordium and by a subpopulation of exocrine cells but not by endocrine cells. These findings raised the possibility that the pancreatic epithelium is heterogeneous and comprised of subpopulations of exocrine/nestin-positive and endocrine/nestin-negative precursor cells. We examined this issue in two mutant mouse models characterized by protracted expression of several embryonal properties in islet cells. One mutant line comprises mice lacking mature glucagon due to abrogation of proprotein convertase-2 (PC2,/,), responsible for the conversion of proglucagon into glucagon, while the second line consists of mice with a global deletion of the glucagon receptor (Gcgr,/,). We demonstrate that nestin is transiently expressed by acinar cells and by insulin and glucagon cells of islets of both lines of mice. In addition, the lack of glucagon signaling increased nestin mRNA levels in pancreas of mutant embryos and adult mice. We conclude that nestin+ cells located in the pancreatic primordium generate the cells of the endocrine and exocrine lineages. Furthermore, our results suggest that nestin expression is regulated by glucagon signaling. Developmental Dynamics 236:1126,1133, 2007. © 2007 Wiley-Liss, Inc. [source] Analysis of pancreatic endocrine development in GDF11-deficient miceDEVELOPMENTAL DYNAMICS, Issue 11 2006Darwin S. Dichmann Abstract Here, we examine the role of GDF11 in pancreatic development. Using in situ hybridization and reverse transcriptase-polymerase chain reaction analyses, we show that Gdf11 transcripts are expressed in embryonic pancreas epithelium before the secondary transition but decrease rapidly afterward. To determine the function of GDF11 during pancreas development, we analyzed Gdf11,/, mouse embryos. In such embryos, pancreas size is twofold reduced at embryonic day (E) 18 compared with wild-type littermates. Quantification of the different tissue compartments shows a specific hypoplasia of the exocrine compartment, while the endocrine and ductal compartments are unaffected. Notably, NGN3+ endocrine precursor cells are increased fourfold at E18, although the amount of endocrine cells in the pancreas of these animals is unchanged compared with wild-type littermates. Similarly, the maturation of endocrine cells as well as the ratio between ,- and ,-cells appears normal. Developmental Dynamics 235:3016,3025, 2006. © 2006 Wiley-Liss, Inc. [source] Cell proliferation in the developing lateral line system of zebrafish embryosDEVELOPMENTAL DYNAMICS, Issue 2 2005Laurent Laguerre Abstract The sensory organs of the embryonic lateral line system are deposited by migrating primordia that originate in the otic region. Here, we examine the pattern of cell proliferation in the posterior lateral line system. We conclude that three phases of cell proliferation are involved in the generation of this system, separated by two phases of mitotic quiescence. The first phase corresponds to generalized proliferation during gastrulation, followed by a first period of quiescence that may be related to the determination of the lateral line precursor cells. A second phase of proliferation takes place in the placode and migrating primordium. This region is organized in annuli that correspond to the expression of proneural/neurogenic genes. A second period of quiescence follows, corresponding to deposition and differentiation of the sensory organs. The third period of proliferation corresponds to continued renewal of hair cells by division of support cells within each sensory organ. Developmental Dynamics 233:466,472, 2005. © 2005 Wiley-Liss, Inc. [source] Molecular characterization of conditionally immortalized cell lines derived from mouse early embryonic inner earDEVELOPMENTAL DYNAMICS, Issue 4 2004John A. Germiller Abstract Inner ear sensory hair cells (HCs), supporting cells (SCs), and sensory neurons (SNs) are hypothesized to develop from common progenitors in the early embryonic otocyst. Because little is known about the molecular signals that control this lineage specification, we derived a model system of early otic development: conditionally immortalized otocyst (IMO) cell lines from the embryonic day 9.5 Immortomouse. This age is the earliest stage at which the otocyst can easily be separated from surrounding mesenchymal, nervous system, and epithelial cells. At 9.5 days post coitum, there are still pluripotent cells in the otocyst, allowing for the eventual identification of both SN and HC precursors,and possibly an elusive inner ear stem cell. Cell lines derived from primitive precursor cells can also be used as blank canvases for transfections of genes that can affect lineage decisions as the cells differentiate. It is important, therefore, to characterize the "baseline state" of these cell lines in as much detail as possible. We characterized seven representative "precursor-like" IMO cell populations and the uncloned IMO cells, before cell sorting, at the molecular level by polymerase chain reaction (PCR) and immunocytochemistry (IHC), and one line (IMO-2B1) in detail by real-time quantitative PCR and IHC. Many of the phenotypic markers characteristic of differentiated HCs or SCs were detected in IMO-2B1 proliferating cells, as well as during differentiation for up to 30 days in culture. These IMO cell lines represent a unique model system for studying early stages of inner ear development and determining the consequences of affecting key molecular events in their differentiation. Developmental Dynamics 231:815,827, 2004. © 2004 Wiley-Liss, Inc. [source] Bilirubin as a determinant for altered neurogenesis, neuritogenesis, and synaptogenesisDEVELOPMENTAL NEUROBIOLOGY, Issue 9 2009Adelaide Fernandes Abstract Elevated levels of serum unconjugated bilirubin (UCB) in the first weeks of life may lead to long-term neurologic impairment. We previously reported that an early exposure of developing neurons to UCB, in conditions mimicking moderate to severe neonatal jaundice, leads to neuritic atrophy and cell death. Here, we have further analyzed the effect of UCB on nerve cell differentiation and neuronal development, addressing how UCB may affect the viability of undifferentiated neural precursor cells and their fate decisions, as well as the development of hippocampal neurons in terms of dendritic and axonal elongation and branching, the axonal growth cone morphology, and the establishment of dendritic spines and synapses. Our results indicate that UCB reduces the viability of proliferating neural precursors, decreases neurogenesis without affecting astrogliogenesis, and increases cellular dysfunction in differentiating cells. In addition, an early exposure of neurons to UCB decreases the number of dendritic and axonal branches at 3 and 9 days in vitro (DIV), and a higher number of neurons showed a smaller growth cone area. UCB-treated neurons also reveal a decreased density of dendritic spines and synapses at 21 DIV. Such deleterious role of UCB in neuronal differentiation, development, and plasticity may compromise the performance of the brain in later life. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009 [source] Adult neurogenesis in the crayfish brain: Proliferation, migration, and possible origin of precursor cellsDEVELOPMENTAL NEUROBIOLOGY, Issue 7 2009Yi Zhang Abstract The birth of new neurons and their incorporation into functional circuits in the adult brain is a characteristic of many vertebrate and invertebrate organisms, including decapod crustaceans. Precursor cells maintaining life-long proliferation in the brains of crayfish (Procambarus clarkii, Cherax destructor) and clawed lobsters (Homarus americanus) reside within a specialized niche on the ventral surface of the brain; their daughters migrate to two proliferation zones along a stream formed by processes of the niche precursors. Here they divide again, finally producing interneurons in the olfactory pathway. The present studies in P. clarkii explore (1) differential proliferative activity among the niche precursor cells with growth and aging, (2) morphological characteristics of cells in the niche and migratory streams, and (3) aspects of the cell cycle in this lineage. Morphologically symmetrical divisions of neuronal precursor cells were observed in the niche near where the migratory streams emerge, as well as in the streams and proliferation zones. The nuclei of migrating cells elongate and undergo shape changes consistent with nucleokinetic movement. LIS1, a highly conserved dynein-binding protein, is expressed in cells in the migratory stream and neurogenic niche, implicating this protein in the translocation of crustacean brain neuronal precursor cells. Symmetrical divisions of the niche precursors and migration of both daughters raised the question of how the niche precursor pool is replenished. We present here preliminary evidence for an association between vascular cells and the niche precursors, which may relate to the life-long growth and maintenance of the crustacean neurogenic niche. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009 [source] Polysialic acid controls NCAM-induced differentiation of neuronal precursors into calretinin-positive olfactory bulb interneuronsDEVELOPMENTAL NEUROBIOLOGY, Issue 9 2008Iris Röckle Abstract Understanding the mechanisms that regulate neurogenesis is a prerequisite for brain repair approaches based on neuronal precursor cells. One important regulator of postnatal neurogenesis is polysialic acid (polySia), a post-translational modification of the neural cell adhesion molecule NCAM. In the present study, we investigated the role of polySia in differentiation of neuronal precursors isolated from the subventricular zone of early postnatal mice. Removal of polySia promoted neurite induction and selectively enhanced maturation into a calretinin-positive phenotype. Expression of calbindin and Pax6, indicative for other lineages of olfactory bulb interneurons, were not affected. A decrease in the number of TUNEL-positive cells indicated that cell survival was slightly improved by removing polySia. Time lapse imaging revealed the absence of chain migration and low cell motility, in the presence and absence of polySia. The changes in survival and differentiation, therefore, could be dissected from the well-known function of polySia as a promoter of precursor migration. The differentiation response was mimicked by exposure of cells to soluble or substrate-bound NCAM and prevented by the C3d-peptide, a synthetic ligand blocking NCAM interactions. Moreover, a higher degree of differentiation was observed in cultures from polysialyltransferase-depleted mice and after NCAM exposure of precursors from NCAM-knockout mice demonstrating that the NCAM function is mediated via heterophilic binding partners. In conclusion, these data reveal that polySia controls instructive NCAM signals, which direct the differentiation of subventricular zone-derived precursors towards the calretinin-positive phenotype of olfactory bulb interneurons. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008 [source] Neural precursor cells from a fatal human motoneuron disease differentiate despite aberrant gene expressionDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2007Niklas Pakkasjärvi Abstract Precursor cells of the human central nervous system can be cultured in vitro to reveal pathogenesis of diseases or developmental disorders. Here, we have studied the biology of neural precursor cells (NPCs) from patients of lethal congenital contracture syndrome (LCCS), a severe motoneuron disease leading to prenatal death before the 32nd gestational week. LCCS fetuses are immobile because of a motoneuron defect, seen as degeneration of the anterior horn and descending tracts of the developing spinal cord. The genetic defect for the syndrome is unknown. We show that NPCs isolated postmortem from LCCS fetuses grow and are maintained in culture, but display increased cell cycle activity. Global transcript analysis of undifferentiated LCCS precursor cells present with changes in EGF-related signaling when compared with healthy age-matched human controls. Further, we show that LCCS-derived NPCs differentiate into cells of neuronal and glial lineage and that the initial differentiation is not accompanied by overt apoptosis. Cells expressing markers Islet-1 and Hb9 are also generated from the LCCS NPCs, suggesting that the pathogenic mechanism of LCCS does not directly affect the differentiation capacity or survival of the cells, but the absence of motoneurons in LCCS may be caused by a noncell autonomous mechanism. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007 [source] FLT3 Antibody-based therapy for leukemiaDRUG DEVELOPMENT RESEARCH, Issue 6 2006Yiwen Li Abstract Technological advances in antibody generation and production have facilitated recent clinical and commercial success with antibody-based cancer therapeutics. The class III receptor tyrosine kinase FLT3 is highly expressed on the blast cells in most cases of acute myelogenous leukemia (AML) and B-cell acute lymphoblastic leukemia (ALL). Activating mutations of FLT3 are detected in approximately 37% AML patients. FLT3 expression in normal tissue is limited to myeloid and B-cell precursor cells. Therefore, over-expressed or mutated FLT3 is an attractive target for therapeutic intervention using monoclonal antibodies. This review will discuss recent progress in the development of anti-FLT3 antibodies as well as their therapeutic potentials in the treatment of AML and other hematological malignancies. Drug Dev. Res. 67:495,500, 2006. © 2006 Wiley-Liss, Inc. [source] Proteomic analysis of osteogenic differentiation of dental follicle precursor cellsELECTROPHORESIS, Issue 7 2009Christian Morsczeck Abstract Recently, there has been an increased interest in unravelling the molecular mechanisms and cellular pathways controlling the differentiation and proliferation of human stem cell lines. Proteome analysis has proven to be an effective approach to comprehensive analysis of the regulatory network of differentiation. In the present study we applied 2-DE combined with capillary-LC-MS/MS analysis to profile differentially regulated proteins upon differentiation of dental follicle precursor cells (DFPCs). Out of 115 differentially regulated proteins, glutamine synthetase, lysosomal proteinase cathepsin B proteins, plastin 3 T-isoform, beta-actin, superoxide dismutases, and transgelin were found to be highly up-regulated, whereas cofilin-1, pro-alpha 1 collagen, destrin, prolyl 4-hydrolase and dihydrolipoamide dehydrogenase were found to be highly down-regulated. The group of up-regulated proteins is associated with actin-bundling and defence against oxidative cellular stress, whereas down-regulated proteins were associated with collagen biosynthesis. Bioinformatic analyses of the entire data set confirmed these findings that represent significant steps towards the understanding of DFPC differentiation. The bioinformatic analyses suggest that proteins associated with cell cycle progression and protein metabolism were down-regulated and proteins involved in catabolism, cell motility and biological quality were up-regulated. These results display the general physiological state of DFPCs before and after osteogenic differentiation. We also identified regulatory proteins, such as the transcription factors TP53 and Sp-1, associated with the differentiation process. Further studies will investigate the impact of identified regulatory proteins for cell proliferation and osteogenic differentiation in DFPCs. [source] Genetic damage detected in CD-1 mouse pups exposed perinatally to 3,-azido-3,-deoxythymidine and dideoxyinosine via maternal dosing, nursing, and direct gavageENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2004Jack B. Bishop Abstract Human immunodeficiency virus (HIV)-infected pregnant women are administered nucleoside-analogue antiretrovirals to reduce maternal-infant viral transmission. The current protocol recommends treating newborns for 6 additional weeks postpartum. The treatment is effective, but the risk of drug-induced chromosomal damage in neonates remains undefined. We used a mouse model to investigate this concern. In a multigeneration reproductive toxicity study, female CD-1 mice received 3,-azido-3,-deoxythymidine (AZT) and dideoxyinosine (ddI) (50/250, 75/375, 150/750 mg/kg/day AZT/ddI) by gavage twice daily in equal fractions beginning prior to mating and continuing throughout gestation and lactation. Direct pup dosing (same regimen) began on postnatal day (PND) 4. Peripheral blood erythrocytes of male pups were screened for micronuclei, markers of chromosomal damage, on PNDs 1, 4, 8, and 21. Extraordinary increases in micronucleated cells were noted in pups for each treatment group at each sampling time; treated dams exhibited smaller yet significant increases in micronucleated erythrocytes. The frequencies of micronucleated cells in untreated pups were higher than in the untreated dams, and all pups had markedly elevated levels of circulating reticulocytes compared to dams. These observations suggest that fetal and neonatal mouse hematopoietic precursor cells have heightened sensitivity to genotoxic agents, perhaps due to rapid cell proliferation during the perinatal period of development. The amount of genetic damage observed in treated pups raises concern for the potential of similar damage in humans. Investigations of chromosomal integrity in exposed newborns and children are recommended. Environ. Mol. Mutagen. 43:3,9, 2004. © 2004 Wiley-Liss, Inc. [source] Effects of rapamycin on accumulation of , -, , - and , -globin mRNAs in erythroid precursor cells from , -thalassaemia patientsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2006Eitan Fibach Abstract:, We studied the effects of rapamycin on cultures of erythroid progenitors derived from the peripheral blood of 10 , -thalassaemia patients differing widely with respect to their potential to produce foetal haemoglobin (HbF). For this, we employed the two-phase liquid culture procedure for growing erythroid progenitors, high performance liquid chromatography for analysis of HbF production and reverse transcription polymerase chain reaction for quantification of the accumulation of globin mRNAs. The results demonstrated that rapamycin induced an increase of HbF in cultures from all the , -thalassaemia patients studied and an increase of their overall Hb content/cell. The inducing effect of rapamycin was restricted to , -globin mRNA accumulation, being only minor for , -globin and none for , -globin mRNAs. The ability of rapamycin to preferentially increase , -globin mRNA content and production of HbF in erythroid precursor cells from , -thalassaemia patients is of great importance as this agent (also known as sirolimus or rapamune) is already in clinical use as an anti-rejection agent following kidney transplantation. These data suggest that rapamycin warrants further evaluation as a potential therapeutic drug in , -thalassaemia and sickle cell anaemia. [source] Correction: IL-23 promotes osteoclast formation by up-regulation of receptor activator of NF-,B (RANK) expression in myeloid precursor cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2009Li Chen No abstract is available for this article. [source] IFN regulatory factor (IRF) 3/7-dependent and -independent gene induction by mammalian DNA that escapes degradationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2008Yasutaka Okabe Abstract DNase II in macrophages cleaves the DNA of engulfed apoptotic cells and of nuclei expelled from erythroid precursor cells. Macrophages in DNase II-deficient mice accumulate undigested DNA and constitutively produce IFN-, as well as TNF-,. The IFN-, causes severe anemia in the DNase II,/, embryos, which die prenatally. On the other hand, when the DNase II gene is inactivated postnatally, mice develop polyarthritis owing to the TNF-, produced by macrophages. Here, we showed that the IFN-, gene activation in DNase II,/, mice is dependent on IFN regulatory factor (IRF) 3 and 7. Accordingly, DNase II,/,IRF3,/,IRF7,/, mice do not suffer from anemia, but they still produce TNF-,, and age-dependently develop chronic polyarthritis. A microarray analysis of the gene expression in the fetal liver revealed a set of genes that is induced in DNase II,/, mice in an IRF3/IRF7-dependent manner, and another set that is induced independent of these factors. These results indicate that the mammalian chromosomal DNA that accumulates in macrophages due to inefficient degradation activates genes in both IRF3/IRF7-dependent and -independent manners. [source] | ||||||||||||||||||||||||||||