Search results for "PROLIFERATION"
showing 10 items of 1193 documents
The transcription factor Interferon Regulatory Factor 4 is required for the generation of protective effector CD8 + T cells
2013
Robust cytotoxic CD8 + T-cell response is important for immunity to intracellular pathogens. Here, we show that the transcription factor IFN Regulatory Factor 4 (IRF4) is crucial for the protective CD8 + T-cell response to the intracellular bacterium Listeria monocytogenes . IRF4-deficient ( Irf4 −/− ) mice could not clear L. monocytogenes infection and generated decreased numbers of L. monocytogenes -specific CD8 + T cells with impaired effector phenotype and function. Transfer of wild-type CD8 + T cells into Irf4 −/− mice improved bacterial clearance, suggesting an intrinsic defect of CD8 + T cells in Irf4 −/− mice. Following transfer into wild-type recipients, Irf4 −/− CD8 + T cells bec…
Evidence for a common progenitor of epithelial and mesenchymal components of the liver
2013
Tissues of the adult organism maintain the homeostasis and respond to injury by means of progenitor/stem cell compartments capable to give rise to appropriate progeny. In organs composed by histotypes of different embryological origins (e.g. The liver), the tissue turnover may in theory involve different stem/precursor cells able to respond coordinately to physiological or pathological stimuli. In the liver, a progenitor cell compartment, giving rise to hepatocytes and cholangiocytes, can be activated by chronic injury inhibiting hepatocyte proliferation. The precursor compartment guaranteeing turnover of hepatic stellate cells (HSCs) (perisinusoidal cells implicated with the origin of the …
Axonal control of the adult neural stem cell niche.
2014
SummaryThe ventricular-subventricular zone (V-SVZ) is an extensive germinal niche containing neural stem cells (NSCs) in the walls of the lateral ventricles of the adult brain. How the adult brain’s neural activity influences the behavior of adult NSCs remains largely unknown. We show that serotonergic (5HT) axons originating from a small group of neurons in the raphe form an extensive plexus on most of the ventricular walls. Electron microscopy revealed intimate contacts between 5HT axons and NSCs (B1) or ependymal cells (E1) and these cells were labeled by a transsynaptic viral tracer injected into the raphe. B1 cells express the 5HT receptors 2C and 5A. Electrophysiology showed that acti…
Murine muscle engineered from dermal precursors: an in vitro model for skeletal muscle generation, degeneration and fatty infiltration.
2013
Skeletal muscle can be engineered by converting dermal precursors into muscle progenitors and differentiated myocytes. However, the efficiency of muscle development remains relatively low and it is currently unclear if this is due to poor characterization of the myogenic precursors, the protocols used for cell differentiation, or a combination of both. In this study, we characterized myogenic precursors present in murine dermospheres, and evaluated mature myotubes grown in a novel three-dimensional culture system. After 5-7 days of differentiation, we observed isolated, twitching myotubes followed by spontaneous contractions of the entire tissue-engineered muscle construct on an extracellul…
Candida albicans triggers proliferation and differentiation of hematopoietic stem and progenitor cells by a MyD88-dependent signaling.
2009
As TLRs are expressed by hematopoietic stem and progenitor cells, these receptors may play a role in hematopoiesis in response to pathogens during infection. We showed here that inactivated yeasts and hyphae of Candida albicans induce in vitro the proliferation of purified murine hematopoietic stem and progenitor cells (Lin(-)c-Kit(+) Sca-1(+)) as well as their differentiation to lineage positive cells, through a MyD88-dependent pathway. These results indicate that TLR-mediated recognition of C. albicans by hematopoietic stem and progenitor cells may augment the host capability for rapidly replenishing the innate immune system during candidiasis.
Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells.
2007
The cannabinoid system is immunomodulatory and has been targeted as a treatment for the central nervous system (CNS) autoimmune disease multiple sclerosis. Using an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), we investigated the role of the CB(1) and CB(2) cannabinoid receptors in regulating CNS autoimmunity. We found that CB(1) receptor expression by neurons, but not T cells, was required for cannabinoid-mediated EAE suppression. In contrast, CB(2) receptor expression by encephalitogenic T cells was critical for controlling inflammation associated with EAE. CB(2)-deficient T cells in the CNS during EAE exhibited reduced levels of apoptosis, a higher…
Improved synthesis and in vitro evaluation of the cytotoxic profile of oxysterols oxidized at C4 (4α- and 4β-hydroxycholesterol) and C7 (7-ketocholes…
2013
Whereas the biological activities of oxysterols oxidized at C7 (7-ketocholesterol (7KC), 7β-hydroxycholesterol (7β-OHC), 7α-hydroxycholesterol (7α-OHC)) are well documented, those of oxysterols oxidized at C4 (4β-hydroxycholesterol (4β-OHC), 4α-hydroxycholesterol (4α-OHC)) are not well known, especially on the cells of the central nervous system. Therefore, an improved methodology has been validated for 4β-OHC and 4α-OHC synthesis, and the effects on cell viability and cell growth of these molecules were studied on immortalized, tumoral and normal brain cells (158N, C6 and SK-N-BE cells, and mixed primary cultures of astrocytes and oligodendrocytes). Whereas inhibition of cell growth with 7…
Thymidine analogs are transferred from prelabeled donor to host cells in the central nervous system after transplantation: a word of caution
2006
Thymidine analogs, including bromodeoxyuridine, chlorodeoxyuridine, iododeoxyuridine, and tritiated thymidine, label dividing cells by incorporating into DNA during S phase of cell division and are widely employed to identify cells transplanted into the central nervous system. However, the potential for transfer of thymidine analogs from grafted cells to dividing host cells has not been thoroughly tested. We here demonstrate that graft-derived thymidine analogs can become incorporated into host neural precursors and glia. Large numbers of labeled neurons and glia were found 3-12 weeks after transplantation of thymidine analog-labeled live stem cells, suggesting differentiation of grafted ce…
Genetic Cell Ablation Reveals Clusters of Local Self-Renewing Microglia in the Mammalian Central Nervous System
2015
SummaryDuring early embryogenesis, microglia arise from yolk sac progenitors that populate the developing central nervous system (CNS), but how the tissue-resident macrophages are maintained throughout the organism’s lifespan still remains unclear. Here, we describe a system that allows specific, conditional ablation of microglia in adult mice. We found that the microglial compartment was reconstituted within 1 week of depletion. Microglia repopulation relied on CNS-resident cells, independent from bone-marrow-derived precursors. During repopulation, microglia formed clusters of highly proliferative cells that migrated apart once steady state was achieved. Proliferating microglia expressed …
Multiple roles forHoxgenes in segment-specific shaping of CNS lineages
2008
In this article we highlight some of the recently accumulating evidence showing that Hox genes are involved at different steps during the development of neural cell lineages to control segmental patterning of the CNS. In addition to their well-known early role in establishing segmental identities, Hox genes act on neural stem cells and their progeny at various stages during embryonic and postembryonic development to control proliferation, cell fate and/or apoptosis in a segment-specific manner. This leads to differential shaping of serially homologous lineages and thus to structural diversification of segmental CNS units (neuromeres) in adaptation to their specific functional tasks in proce…