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See detailCd28-B7 Costimulatory Blockade by Ctla4ig Delays the Development of Retrovirus-Induced Murine Aids
de Leval, Laurence ULg; Colombi, S.; Debrus, S. et al

in Journal of Virology (1998), 72(6), 5285-90

Mouse AIDS (MAIDS) induced in C57BL/6 mice by infection with a replication-defective retrovirus (Du5H) combines extensive lymphoproliferation and profound immunodeficiency. Although B cells are the main ... [more ▼]

Mouse AIDS (MAIDS) induced in C57BL/6 mice by infection with a replication-defective retrovirus (Du5H) combines extensive lymphoproliferation and profound immunodeficiency. Although B cells are the main target of viral infection, recent research has focused on CD4(+) T cells, the activation of which is a key event in MAIDS induction and progression. A preliminary observation of increased expression of B7 molecules on B cells in MAIDS prompted us to address the possible involvement of the CD28/B7 costimulatory pathway in MAIDS. Mice infected with the MAIDS-inducing viral preparation were treated with murine fusion protein CTLA4Ig (3 x 50 microg/week given intraperitoneally), a competitive inhibitor of physiological CD28-B7 interactions. In CTLA4Ig-treated animals, the onset of the disease was delayed, lymphoproliferation progressed at a much slower rate than in untreated mice, and the loss of in vitro responsiveness to mitogens was reduced. Relative expression of Du5H did not differ between treated and untreated animals. These results suggest that the CD28/B7 costimulatory pathway contributes to MAIDS development. [less ▲]

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See detailCD30-positive peripheral T-cell lymphomas share molecular and phenotypic features
Bisig, B.; de Reyniès, A.; Bonnet, Christophe ULg et al

in Haematologica (2013), 98/n°8

Peripheral T-cell lymphoma, not otherwise specified is a heterogeneous group of aggressive neoplasms with indistinct borders. By gene expression profiling we previously reported unsupervised clusters of ... [more ▼]

Peripheral T-cell lymphoma, not otherwise specified is a heterogeneous group of aggressive neoplasms with indistinct borders. By gene expression profiling we previously reported unsupervised clusters of peripheral T-cell lymphomas, not otherwise specified correlating with CD30 expression. In this work we extended the analysis of peripheral T-cell lymphoma molecular profiles to prototypical CD30+ peripheral T-cell lymphomas (anaplastic large cell lymphomas), and validated mRNA expression profiles at the protein level. Existing transcriptomic datasets from peripheral T-cell lymphomas, not otherwise specified and anaplastic large cell lymphomas were reanalyzed. Twenty-one markers were selected for immunohistochemical validation on 80 peripheral T-cell lymphoma samples (not otherwise specified, CD30+ and CD30–; anaplastic large cell lymphomas, ALK+ and ALK–), and differences between subgroups were assessed. Clinical follow-up was recorded. Compared to CD30– tumors, CD30+ peripheral T-cell lymphomas, not otherwise specified were significantly enriched in ALK– anaplastic large cell lymphoma-related genes. By immunohistochemistry, CD30+ peripheral T-cell lymphomas, not otherwise specified differed significantly from CD30– samples [down-regulated expression of T-cell receptor-associated proximal tyrosine kinases (Lck, Fyn, Itk) and of proteins involved in T-cell differentiation/activation (CD69, ICOS, CD52, NFATc2); upregulation of JunB and MUM1], while overlapping with anaplastic large cell lymphomas. CD30– peripheral T-cell lymphomas, not otherwise specified tended to have an inferior clinical outcome compared to the CD30+ subgroups. In conclusion, we show molecular and phenotypic features common to CD30+ peripheral T-cell lymphomas, and significant differences between CD30– and CD30+ peripheral T-cell lymphomas, not otherwise specified, suggesting that CD30 expression might delineate two biologically distinct subgroups. [less ▲]

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See detailCD34+ cell dose predicts costs after autologous peripheral blood stem cell transplantation for breast cancer.
Baron, Frédéric ULg; Copizza, Sandra; Baudoux, Etienne ULg et al

in Haematologica (2004), 89(9), 1146-8

We assessed the effect of CD34+ cell dose on costs in breast cancer patients undergoing autologous peripheral blood stem cell (PBSC) transplantation. Mean hospitalization costs were 26,992.9+/-9582.9 for ... [more ▼]

We assessed the effect of CD34+ cell dose on costs in breast cancer patients undergoing autologous peripheral blood stem cell (PBSC) transplantation. Mean hospitalization costs were 26,992.9+/-9582.9 for patients receiving a CD34+ cell dose <5 x 10(6) cells/kg versus 22,339.4+/- 5471.1 for those receiving >5 x 10(6) CD34+ cells/kg (p=0.0065). [less ▲]

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See detailCD36: linking lipids to the NLRP3 inflammasome, atherogenesis and atherothrombosis
Oury, Cécile ULg

in Cellular & Molecular Immunology (2014), 11

Uptake of the atherogenic lipid mediator oxLDL by CD36 results in the formation of intracellular cholesterol crystals that caused lyso¬somal destabilization and NLRP3 activation. oxLDL not only primes ... [more ▼]

Uptake of the atherogenic lipid mediator oxLDL by CD36 results in the formation of intracellular cholesterol crystals that caused lyso¬somal destabilization and NLRP3 activation. oxLDL not only primes, via a NF-κB-dependent pathway, but also activates NLRP3. CD36-mediated inflammasome activation provides an early pathogenic pathway that links cholesterol accumulation to the chronic inflammatory process of atherosclerosis. During atherogenesis, activated or injured endothelial cells, leucocytes and platelets release ATP that acts in a paracrine manner to transduce sterile inflammatory signals. Among these signals, P2X7 receptors mediate K+ efflux leading to NLRP3 activation. Since ATP assembles ASC complexes in oxLDL-treated macrophages, P2X7 receptors and CD36 may cooperate in vivo to activate NLRP3 inflammasome, contributing to plaque formation. Besides macrophages, CD36 is expressed on platelets where it mediates oxLDL-dependent platelet activation and potentially further IL-1β release. P2X7 receptors contributes to protein disulfide isomerase (PDI) tissue factor-dependent thrombosis. Consequently, both CD36 and P2X7 receptors may be involved in atherothrombosis upon plaque rupture. [less ▲]

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See detailCD39 is highly involved in mediating the suppression activity of tumor-infiltrating CD8+ T regulatory lymphocytes.
Conteduca, Giuseppina ULg

in Cancer Immunology, Immunotherapy (2013), 62(5), 851-62

CD39 is an ectoenzyme, present on different immune cell subsets, which mediates immunosuppressive functions catalyzing ATP degradation. It is not known whether CD39 is expressed and implicated in the ... [more ▼]

CD39 is an ectoenzyme, present on different immune cell subsets, which mediates immunosuppressive functions catalyzing ATP degradation. It is not known whether CD39 is expressed and implicated in the activity of CD8+ regulatory T lymphocytes (Treg). In this study, CD39 expression and function was analyzed in both CD8+ and CD4+CD25(hi) Treg from the peripheral blood of healthy donors as well as from tumor specimens. CD39 was found expressed by both CD8+ (from the majority of healthy donors and tumor patients) and CD4+CD25(hi) Treg, and CD39 expression correlated with suppression activity mediated by CD8+ Treg. Importantly, CD39 counteraction remarkably inhibited the suppression activity of CD8+ Treg (both from peripheral blood and tumor microenvironment) suggesting that CD39-mediated inhibition constitutes a prevalent hallmark of their function. Collectively, these findings, unveiling a new mechanism of action for CD8+ Treg, provide new knowledge on intratumoral molecular pathways related to tumor immune escape, which could be exploited in the future for designing new biological tools for anticancer immune intervention. [less ▲]

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See detailCD4+ T cells determine the ability of spleen cells from F1 hybrid mice to induce neonatal tolerance to alloantigens and autoimmunity in parental mice
Gonzales, M.; Schurmans, Stéphane ULg; Ramos, A. et al

in European Journal of Immunology (1995), 25

Spleen cells from F1 hybrid mice injected into newborn parental mice induce a state of cytolytic unresponsiveness to the corresponding alloantigens. However, these mice develop a transient autoimmune ... [more ▼]

Spleen cells from F1 hybrid mice injected into newborn parental mice induce a state of cytolytic unresponsiveness to the corresponding alloantigens. However, these mice develop a transient autoimmune syndrome characterized by the production of multiple autoantibodies and glomerulonephritis. Previous reports indicated that the depletion of F1 donor T cells, shortly prior the injection into parental mice, does not interfere with any of these events. Here, we have explored whether the continuous absence of T cells in F1 mice influences the ability of their spleen cells to induce neonatal tolerance to alloantigens and the associated autoimmune manifestations. Our results revealed that spleen cells from athymic (BALB/c x C57BL/6) F1 hybrid (CB6F1) nu/nu mice or from euthymic CB6F1 mice depleted from birth of CD4+ T cells, but not of CD8+ T cells, are unable to induce neonatal tolerance to alloantigens and autoimmune manifestations. By contrast, the partial reconstitution of T cells in CB6F1 nu/nu mice, after the neonatal graft of a syngeneic thymus, restored the capacity of spleen cells from these mice to induce tolerance and autoimmunity when injected into newborn BALB/c mice. These results demonstrate that the functional defect of spleen cells from athymic CB6F1 nu/nu mice to induce neonatal tolerance to alloantigens is directly related to the long-term absence of mature CD4+ T cells. Interestingly, a new increase in the titers of anti-DNA Ab was observed when spleen cells from athymic CB6F1 nu/nu mice were injected into adult BALB/c mice that had been tolerized at birth with normal CB6F1 spleen cells. This finding indicates that B cells from CB6F1 nu/nu mice recover their capacity to interact with alloreactive Th2 cells when they are placed into mice having functional CD4+ T cells. These data indicate that the continuous absence of CD4+ T cells causes a reversible functional defect in F1 spleen cells that determines their inability to induce neonatal tolerance and autoimmunity [less ▲]

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See detailCD40 engagement enhances eosinophil survival through induction of cellular inhibitor of apoptosis protein 2 expression: possible involvement in allergic inflammation
Bureau, Fabrice ULg; Seumois, G.; Jaspar, F. et al

in Pflügers Archiv : European Journal of Physiology (2002), 443

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See detailCD40 engagement enhances eosinophil survival through induction of cellular inhibitor of apoptosis protein 2 expression: Possible involvement in allergic inflammation.
Bureau, Fabrice ULg; Seumois, Gregory; Jaspar, Fabrice et al

in Journal of Allergy and Clinical Immunology (The) (2002), 110(3), 443-9

BACKGROUND: CD40 engagement enhances eosinophil survival, suggesting a role for this receptor in the development of eosinophilia. OBJECTIVE: We examined whether CD40 enhances eosinophil survival by ... [more ▼]

BACKGROUND: CD40 engagement enhances eosinophil survival, suggesting a role for this receptor in the development of eosinophilia. OBJECTIVE: We examined whether CD40 enhances eosinophil survival by inducing the expression of antiapoptotic proteins. Three members of the inhibitor of apoptosis protein (IAP) family, namely cellular (c)-IAP1, c-IAP2, and XIAP, and 2 antiapoptotic proteins of the Bcl-2 family, namely Bcl-x(L) and Bfl-1/A1, were investigated. METHODS: Blood and sputum were obtained from healthy subjects and atopic asthmatic patients. Blood eosinophils were isolated by means of magnetic selection. Expression of CD40, IAPs, and Bcl-2 proteins was investigated by using flow cytometry, immunoblotting, or both. CD40 stimulation was achieved with agonistic antibodies or soluble ligands. Apoptosis was assessed by staining with propidium iodide and FITC-conjugated annexin-V. c-IAP2 expression was inhibited with antisense oligonucleotides. RESULTS: Freshly isolated eosinophils from healthy and asthmatic patients did not express CD40. Conversely, eosinophils expressed CD40 spontaneously when cultured for 48 hours. At this time point, CD40 stimulation significantly delayed eosinophil apoptosis. Inhibition of eosinophil apoptosis was accompanied by induction of c-IAP2 but not c-IAP1, XIAP, Bcl-x(L), or Bfl-1/A1 expression. Antisense knockdown of c-iap2 abolished CD40-induced enhancement of eosinophil survival. Sputum cells from asthmatic patients, unlike those from healthy subjects, substantially expressed CD40 and c-IAP2. Moreover, a strong correlation was found between the percentage of eosinophils in the sputum from asthmatic patients and the sputum level of CD40 and c-IAP2 expression. CONCLUSION: The results demonstrate that CD40 engagement enhances eosinophil survival through induction of c-IAP2 expression and suggest a role for this mechanism in allergic inflammation. [less ▲]

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See detailCD44v6 expression is an independent prognostic factor in node-negative FIGO stage IB cervical carcinoma.
Speiser, P.; KRIDELKA, Frédéric ULg; Tempfer, C. et al

in International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society (1999), 9(2), 160-165

Adhesion molecules such as CD44 play an important role in the metastatic cascade by mediating tumor cell interaction with the endothelium and the subendothelial matrix. As a so-called "lymphocyte homing ... [more ▼]

Adhesion molecules such as CD44 play an important role in the metastatic cascade by mediating tumor cell interaction with the endothelium and the subendothelial matrix. As a so-called "lymphocyte homing receptor," CD44 is physiologically involved in migration of circulating lymphocytes to lymphatic tissue. In the present study, we investigated the expression of CD44v3 and v6 in 237 patients with stage IB, N0 cervical carcinoma by means of immunohistochemistry. These results were correlated with the GOG score and other prognostic variables. Median follow-up was 82.6 months (39-110 months). Thirty-nine patients recurred and 35 died from disease within the observation period. In univariate analysis, the GOG score, histologic subtype, and CD44v6 expression were statistically significant predictors for poor overall survival (OS). In multivariate (Cox regression) analysis, the GOG score (< 40 vs. 40-120, RR: 1.37 (95% CI: 1.10-1.71); 40-120 vs. > 120, RR: 2.23 (95% CI: 1.28-3.88); P = 0.004), histologic subtype (adenosquamous carcinomas) (RR: 4.56 (95% CI: 1.49-13.92), P = 0.007) and CD44v6 expression (RR: 2.42 (95% CI: 1.14-5.10), P = 0.021) were independent predictors for poor OS. The expression of CD44v3 did not correlate with prognosis. Furthermore we found a strong correlation between CD44v6 expression and lymphovascular space invasion (LVSI) (chi2 = 17.01, P = 0.0001). Tumor expansion into the loco-regional lymphatic system is the preferred way of tumor spread in cervical carcinoma. The strong correlation of CD44v6 with LVSI produces a significant degree of suspicion that cervical carcinoma cells expressing CD44v6 could, by mimicking lymphocytes, exploit their pathways. [less ▲]

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See detailCD68 and Factor XIIIa expressions in granular-cell tumor of the skin
Nikkels, Arjen ULg; Arrese Estrada, Jorge ULg; Pierard-Franchimont, Claudine ULg et al

in Dermatology : International Journal for Clinical & Investigative Dermatology (1993), 186(2), 106-108

Immunohistochemical and electron microscopic studies support a Schwann cell origin for most of the granular-cell tumors of the skin. We studied 9 granular-cell tumors by immunohistochemistry, using ... [more ▼]

Immunohistochemical and electron microscopic studies support a Schwann cell origin for most of the granular-cell tumors of the skin. We studied 9 granular-cell tumors by immunohistochemistry, using antibodies to CD68, S-100 proteins, factor XIIIa, L1 antigen, desmin and vimentin. The CD68 monocyte-macrophage-associated lysosomal antigen was expressed in granular cells which however had no Mac 387 reactivity. The 'satellite fibroblasts' were factor XIIIa-positive similarly to dendrocytes and perineurial cells. Our study reveals the lack of specificity of CD68 antibody to identify macrophages. It also presents granular cell tumor of the skin as an exception in the group of schwannomas by the presence of factor XIIIa-positive cells inside the neoplasm. [less ▲]

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See detailCdc42 downregulates MMP-1 expression by inhibiting the ERK1/2 pathway.
Deroanne, Christophe ULg; Hamelryckx, Delphine; Ho, Thi Thanh Giang ULg et al

in Journal of Cell Science (2005), 118(Pt 6), 1173-83

The small GTPases of the Rho family are key intermediates in cellular signalling triggered by activated cell-adhesion receptors. In this study, we took advantage of RNA interference (RNAi) using small ... [more ▼]

The small GTPases of the Rho family are key intermediates in cellular signalling triggered by activated cell-adhesion receptors. In this study, we took advantage of RNA interference (RNAi) using small interfering RNAs (siRNAs) to define the roles of the best-characterized members of the RhoGTPase family, RhoA, Rac1 and Cdc42, in the control of MMP-1, MMP-2 and type-I-collagen expression in normal human skin fibroblasts (HSFs). A specific and long-lasting repression, up to 7 days after transfection, of the three GTPases was achieved by transient transfection of specific siRNA. The silencing of Cdc42, but not that of RhoA or Rac1, induced a 15-fold increase in MMP-1 secretion. This upregulation was confirmed at the mRNA level and observed with two different siRNAs targeting Cdc42. Such a regulation was also observed in various human cell lines and was rescued by re-expressing wild-type Cdc42 encoded by a construct bearing silent mutations impeding its recognition by the siRNA. By contrast, MMP-2 and type-I-collagen expression was not affected by the individual silencing of each Rho GTPase. Cytokine protein array, enzyme-linked immunosorbent assays and reverse-transcription PCR measurements revealed that ablation of Cdc42 induced an overexpression of interleukin 8 and MCP-1. Although these cytokines are known to induce the expression of MMP-1, we showed that they were not involved in the Cdc42-mediated upregulation of MMP-1. Silencing of Cdc42 also induced an increased phosphorylation of ERK1/2 and p38 MAP kinase. The use of chemical inhibitors on Cdc42-ablated cells revealed that the upregulation of MMP-1 is dependent on the ERK1/2 pathways, whereas the p38 MAP kinase pathway displayed an inhibitory role. Simultaneous knock-down of two or three Rho GTPases allowed us to demonstrate that the RhoA-ROCK pathway was not involved in this regulation but that the silencing of Rac1 reduced the effect of Cdc42 suppression. These data suggest that, in vivo, when cell/extracellular-matrix interactions via integrins induce cytoskeleton organization, MMP-1 expression is maintained at a low level by Cdc42 via a repression of the Rac1 and ERK1/2 pathways. Therefore, Cdc42 contributes to ECM homeostasis and connective tissue integrity. [less ▲]

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See detailCdI2 structure type as potential thermoelectric materials: Synthesis and high temperature thermoelectric properties of the solid solution TiSxSe2−x
Franck, Gascoin; Nunna, Raghavendra ULg; Emmanuel, Guilmeau et al

in Journal of Alloys & Compounds (2012), 521

Polycrystalline samples of the solid solution TiSxSe2−x with x varying from 0 to 2 were prepared using direct high temperature reaction of stoichiometric amounts of the elements. Rietveld refinements of ... [more ▼]

Polycrystalline samples of the solid solution TiSxSe2−x with x varying from 0 to 2 were prepared using direct high temperature reaction of stoichiometric amounts of the elements. Rietveld refinements of powder X-ray diffraction data are consistent with the existence of a full solid solution. High temperature Seebeck coefficient, electrical resistivity and thermal diffusivity measurements were performed on pellets densified by spark plasma sintering. These measurements reveal that along the solid solution the transport properties vary from the rather metallic and p-type character of TiSe2 to the semiconducting and n-type of TiS2. This change of conduction regime is responsible for the peculiar evolutions of transport properties of TiS0.5Se1.5 with increasing temperature that vary somewhat differently than that of the other members of the solid solution. As expected, the disorder generated by the mixed occupancy of the S and Se on the anionic site is responsible for the diminution of the lattice thermal conductivity. A maximum zT above 0.4 at 400 °C is reached for TiS1.5Se0.5. [less ▲]

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See detailCdk1 is a critical mediator of ischemic/hypoxic neuronal death
Vandenbosch, Renaud ULg

Conference (2016, June 20)

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See detailCdk2 is critical for proliferation and self-renewal of neural progenitor cells in the adult subventricular zone
Jablonska, Beata; Aguirre, Adan A.; Vandenbosch, Renaud ULg et al

in Journal of Cell Biology (2007), 179(6), 1231-1245

We investigated the function of cyclin-dependent kinase 2 (Cdk2) in neural progenitor cells during postnatal development. Chondroitin sulfate proteoglycan (NG2)-expressing progenitor cells of the ... [more ▼]

We investigated the function of cyclin-dependent kinase 2 (Cdk2) in neural progenitor cells during postnatal development. Chondroitin sulfate proteoglycan (NG2)-expressing progenitor cells of the subventricular zone (SVZ) show no significant difference in density and proliferation between Cdk2(-/-) and wild-type mice at perinatal ages and are reduced only in adult Cdk2(-/-) mice. Adult Cdk2(-/-) SVZ cells in culture display decreased self-renewal capacity and enhanced differentiation. Compensatory mechanisms in perinatal Cdk2(-/-) SVZ cells, which persist until postnatal day 15, involve increased Cdk4 expression that results in retinoblastoma protein inactivation. A subsequent decline in Cdk4 activity to wild-type levels in postnatal day 28 Cdk2(-/-) cells coincides with lower NG2(+) proliferation and self-renewal capacity similar to adult levels. Cdk4 silencing in perinatal Cdk2(-/-) SVZ cells abolishes Cdk4 up-regulation and reduces cell proliferation and self-renewal to adult levels. Conversely, Cdk4 overexpression in adult SVZ cells restores proliferative capacity to wildtype levels. Thus, although Cdk2 is functionally redundant in perinatal SVZ, it is important for adult progenitor cell proliferation and self-renewal through age-dependent regulation of Cdk4. [less ▲]

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See detailCdk2 Is Dispensable for Adult Hippocampal Neurogenesis
Vandenbosch, Renaud ULg; Borgs, Laurence ULg; Beukelaers, Pierre ULg et al

in Cell Cycle (Georgetown, Tex.) (2007), 6(24), 3065-9

Granule neurons of the dentate gyrus (DG) of the hippocampus undergo continuous renewal throughout life. Among cell cycle regulators, cyclin-dependent kinase 2 (Cdk2) is considered as a major regulator of ... [more ▼]

Granule neurons of the dentate gyrus (DG) of the hippocampus undergo continuous renewal throughout life. Among cell cycle regulators, cyclin-dependent kinase 2 (Cdk2) is considered as a major regulator of S-phase entry. We used Cdk2-deficient mice to decipher the requirement of Cdk2 for the generation of new neurons in the adult hippocampus. The quantification of cell cycle markers first revealed that the lack of Cdk2 activity does not influence spontaneous or seizure-induced proliferation of neural progenitor cells (NPC) in the adult DG. Using bromodeoxyuridine incorporation assays, we showed that the number of mature newborn granule neurons generated de novo was similar in both wild-type (WT) and Cdk2-deficient adult mice. Moreover, the apparent lack of cell output reduction in Cdk2(-/-) mice DG did not result from a reduction in apoptosis of newborn granule cells as analyzed by TUNEL assays. Our results therefore suggest that Cdk2 is dispensable for NPC proliferation, differentiation and survival of adult-born DG granule neurons in vivo. These data emphasize that functional redundancies between Cdks also occur in the adult brain at the level of neural progenitor cell cycle regulation during hippocampal neurogenesis. [less ▲]

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See detailCdk2 loss accelerates precursor differentiation and remyelination in the adult central nervous system.
Caillava, Céline; Vandenbosch, Renaud ULg; Jablonska, Beata et al

in Journal of Cell Biology (2011), 193(2), 397-407

The specific functions of intrinsic regulators of oligodendrocyte progenitor cell (OPC) division are poorly understood. Type 2 cyclin-dependent kinase (Cdk2) controls cell cycle progression of OPCs, but ... [more ▼]

The specific functions of intrinsic regulators of oligodendrocyte progenitor cell (OPC) division are poorly understood. Type 2 cyclin-dependent kinase (Cdk2) controls cell cycle progression of OPCs, but whether it acts during myelination and repair of demyelinating lesions remains unexplored. Here, we took advantage of a viable Cdk2(-/-) mutant mouse to investigate the function of this cell cycle regulator in OPC proliferation and differentiation in normal and pathological conditions. During central nervous system (CNS) development, Cdk2 loss does not affect OPC cell cycle, oligodendrocyte cell numbers, or myelination. However, in response to CNS demyelination, it clearly alters adult OPC renewal, cell cycle exit, and differentiation. Importantly, Cdk2 loss accelerates CNS remyelination of demyelinated axons. Thus, Cdk2 is dispensable for myelination but is important for adult OPC renewal, and could be one of the underlying mechanisms that drive adult progenitors to differentiate and thus regenerate myelin. [less ▲]

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See detailCdk6-dependent regulation of g(1) length controls adult neurogenesis.
Beukelaers, Pierre; Vandenbosch, Renaud ULg; Caron, Nicolas ULg et al

in Stem Cells (2011), 29(4), 713-24

The presence of neurogenic precursors in the adult mammalian brain is now widely accepted, but the mechanisms coupling their proliferation with the onset of neuronal differentiation remain unknown. Here ... [more ▼]

The presence of neurogenic precursors in the adult mammalian brain is now widely accepted, but the mechanisms coupling their proliferation with the onset of neuronal differentiation remain unknown. Here, we unravel the major contribution of the G(1) regulator cyclin-dependent kinase 6 (Cdk6) to adult neurogenesis. We found that Cdk6 was essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Specifically, Cdk6 deficiency prevents the expansion of neuronally committed precursors by lengthening G(1) phase duration, reducing concomitantly the production of newborn neurons. Altogether, our data support G(1) length as an essential regulator of the switch between proliferation and neuronal differentiation in the adult brain and Cdk6 as one intrinsic key molecular regulator of this process. STEM Cells 2011;29:713-724. [less ▲]

Detailed reference viewed: 64 (34 ULg)