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Anne Baron-van Evercooren - One of the best experts on this subject based on the ideXlab platform.

  • Beneficial contribution of induced pluripotent stem cell-progeny to Connexin 47 dynamics during demyelination-remyelination
    Glia, 2020
    Co-Authors: Sabah Mozafari, Cyrille Deboux, Cecilia Laterza, Marc Ehrlich, Tanja Kuhlmann, Gianvito Martino, Anne Baron-van Evercooren
    Abstract:

    Oligodendrocytes are extensively coupled to astrocytes, a phenomenon ensuring glial homeostasis and maintenance of central nervous system myelin. Molecular disruption of this communication occurs in demyelinating diseases such as multiple sclerosis. Less is known about the vulnerability and reconstruction of the panglial network during adult demyelination‐remyelination. Here, we took advantage of lysolcithin‐induced demyelination to investigate the expression dynamics of the oligodendrocyte specific Connexin 47 (Cx47) and to some extent that of astrocyte Cx43, and whether this dynamic could be modulated by grafted induced pluripotent stem cell (iPSC)‐neural progeny. Our data show that disruption of Cx43‐Cx47 mediated hetero‐cellular gap‐junction intercellular communication following demyelination is larger in size than demyelination. Loss of Cx47 expression is timely rescued during remyelination and accelerated by the grafted neural precursors. Moreover, mouse and human iPSC‐derived oligodendrocytes express Cx47, which co‐labels with astrocyte Cx43, indicating their integration into the panglial network. These data suggest that in rodents, full lesion repair following transplantation occurs by panglial reconstruction in addition to remyelination. Targeting panglial elements by cell therapy or pharmacological compounds may help accelerating or stabilizing re/myelination in myelin disorders.

Sabah Mozafari - One of the best experts on this subject based on the ideXlab platform.

  • Beneficial contribution of induced pluripotent stem cell-progeny to Connexin 47 dynamics during demyelination-remyelination
    Glia, 2020
    Co-Authors: Sabah Mozafari, Cyrille Deboux, Cecilia Laterza, Marc Ehrlich, Tanja Kuhlmann, Gianvito Martino, Anne Baron-van Evercooren
    Abstract:

    Oligodendrocytes are extensively coupled to astrocytes, a phenomenon ensuring glial homeostasis and maintenance of central nervous system myelin. Molecular disruption of this communication occurs in demyelinating diseases such as multiple sclerosis. Less is known about the vulnerability and reconstruction of the panglial network during adult demyelination‐remyelination. Here, we took advantage of lysolcithin‐induced demyelination to investigate the expression dynamics of the oligodendrocyte specific Connexin 47 (Cx47) and to some extent that of astrocyte Cx43, and whether this dynamic could be modulated by grafted induced pluripotent stem cell (iPSC)‐neural progeny. Our data show that disruption of Cx43‐Cx47 mediated hetero‐cellular gap‐junction intercellular communication following demyelination is larger in size than demyelination. Loss of Cx47 expression is timely rescued during remyelination and accelerated by the grafted neural precursors. Moreover, mouse and human iPSC‐derived oligodendrocytes express Cx47, which co‐labels with astrocyte Cx43, indicating their integration into the panglial network. These data suggest that in rodents, full lesion repair following transplantation occurs by panglial reconstruction in addition to remyelination. Targeting panglial elements by cell therapy or pharmacological compounds may help accelerating or stabilizing re/myelination in myelin disorders.

  • beneficial contribution of ipsc progeny to Connexin 47 dynamics during demyelination remyelination
    bioRxiv, 2020
    Co-Authors: Sabah Mozafari, Cyrille Deboux, Cecilia Laterza, Marc Ehrlich, Tanja Kuhlmann, Gianvito Martino, Anne Baronvan Evercooren
    Abstract:

    Abstract Oligodendrocytes are extensively coupled to astrocytes, a phenomenon ensuring glial homeostasis and maintenance of CNS myelin. Molecular disruption of this communication occurs in demyelinating diseases such as multiple sclerosis. Less is known about the vulnerability and reconstruction of the panglial network during adult demyelination-remyelination. Here, we took advantage of LPC-induced demyelination to investigate the expression dynamics of the oligodendrocyte specific Connexin 47 (Cx47) and whether this dynamic could be modulated by grafted iPSC-neural progeny. Our data show that deconstruction of the panglial network following demyelination is larger in size than demyelination. Loss of Cx47 expression is timely rescued during remyelination and accelerated by the grafted neural precursors. Moreover, mouse and human iPS-derived oligodendrocytes express Cx47, which co-labels with astrocyte Cx43, indicating their integration into the panglial network. These data suggest that full lesion repair following transplantation occurs by panglial reconstruction in addition to remyelination. Targeting panglial elements by cell therapy or pharmacological compounds may help accelerating or stabilizing re/myelination in myelin disorders.

Y Peng - One of the best experts on this subject based on the ideXlab platform.

  • astrocytes induce proliferation of oligodendrocyte progenitor cells via Connexin 47 mediated activation of chi3l1 expression
    European Review for Medical and Pharmacological Sciences, 2019
    Co-Authors: Lu Jiang, W J Zhang, Y Tang, Y Peng
    Abstract:

    Objective Demyelinating neurodegenerative diseases are some of the most important neurological diseases that threaten the health of the elderly. Astrocytes (ASTs) play an important role in the regulation of the growth and development of oligodendrocytes (OLs) and oligodendrocyte progenitor cells (OPCs), which participate in remyelination. This study investigated the mechanism by which ASTs promote the proliferation of OPCs via Connexin 47 (Cx47) in OPCs. Materials and methods Under direct-contact co-culture conditions, we performed Cx47 siRNA interference in ASTs and OPCs and tested the cell proliferation ability by flow cytometry and with 5-ethynyl-20-deoxyuridine (EdU). We then detected Chi3l1 expression by Western blotting and immunofluorescence. Next, after the addition of exogenous Chi3l1 protein to OPCs under monoculture conditions, we tested the cell proliferation ability by flow cytometry and EdU. Results After siRNA interference with Cx47, the expression of Chi3l1 decreased from 1.10±0.91 to 0.30±0.08, and the proportion of new OPCs decreased from 48.7±3.8% to 28.4±6.6%. Moreover, upon addition of exogenous Chi3l1 protein under OPCs mono-culture conditions, the expression of cyclin D1 increased from 0.68±0.09 to 1.16±0.14, leading to an increased number of OPCs in the S phase, from 7.37±1.38% to 13.55±1.60%. Conclusions Cx47/Chi3l1 plays an important role in the promotion of OPCs proliferation by ASTs. ASTs can promote the expression of Chi3l1 via Cx47 in OPCs, and then activate the expression of cyclin D1 and regulate the cell cycle of OPCs, thereby promoting cell proliferation. This study provides a new target for the treatment of neurodegenerative diseases.

  • astrocytes induce proliferation of oligodendrocyte progenitor cells via Connexin 47 mediated activation of the erk id4 pathway
    Cell Cycle, 2017
    Co-Authors: Zhaoyu Liu, Lu Jiang, Y Tang, Shang Wang, Yi Chen, Xiaoyan Gao, Y Peng
    Abstract:

    The proliferative ability of oligodendrocyte progenitor cells (OPCs) varied markedly under different culture conditions. Astrocytes (ASTs) have been verified to play a major role in regulating the proliferation of OPCs through direct contact. However, the mechanisms have not been fully clarified. To investigate the effect and mechanism under AST and OPC co-culture conditions, we analyzed all Connexins comprehensively in OPCs under OPC mono-culture, AST-secreted cell factor co-culture and AST-OPC direct-contact co-culture, and found that significantly differentially expressed Cx47 was the most significant. To assess whether Cx47 plays a role in proliferation, Cx47 siRNA were conducted. The result indicates that the cell cycle of OPCs was changed, and the cell proliferation was markedly inhibited. Kyoto Encyclopedia of Genes and Genomes (KEGG) predictive analysis suggested that Cx47 regulate cell cycle and proliferation by Ca2+ activation of ERK1/2. To verify the prediction, flow cytometry, confocal microscopy, 5-ethynyl-2'-deoxyuridine (EdU), polymerase chain reaction (RT-PCR) and western blot were used. The results show that interference of Cx47 led to decreased Ca2+ concentrations, lower p-ERK 1/2 levels, reduced transcription factor inhibitor of DNA binding 4 (Id4) expression, arrested cell cycle and reduced OPCs proliferative ability. Additionally, blocking ERK1/2 signaling caused decreased Id4 expression, arrested cell cycle in G1 phase, and reduced OPCs proliferative ability. In conclusion, ASTs can cause Ca2+ signaling activation, ERK1/2 phosphorylation, and Id4 expression stimulation in OPCs, inducing proliferation of these cells, mainly through Cx47.

Tanja Kuhlmann - One of the best experts on this subject based on the ideXlab platform.

  • Beneficial contribution of induced pluripotent stem cell-progeny to Connexin 47 dynamics during demyelination-remyelination
    Glia, 2020
    Co-Authors: Sabah Mozafari, Cyrille Deboux, Cecilia Laterza, Marc Ehrlich, Tanja Kuhlmann, Gianvito Martino, Anne Baron-van Evercooren
    Abstract:

    Oligodendrocytes are extensively coupled to astrocytes, a phenomenon ensuring glial homeostasis and maintenance of central nervous system myelin. Molecular disruption of this communication occurs in demyelinating diseases such as multiple sclerosis. Less is known about the vulnerability and reconstruction of the panglial network during adult demyelination‐remyelination. Here, we took advantage of lysolcithin‐induced demyelination to investigate the expression dynamics of the oligodendrocyte specific Connexin 47 (Cx47) and to some extent that of astrocyte Cx43, and whether this dynamic could be modulated by grafted induced pluripotent stem cell (iPSC)‐neural progeny. Our data show that disruption of Cx43‐Cx47 mediated hetero‐cellular gap‐junction intercellular communication following demyelination is larger in size than demyelination. Loss of Cx47 expression is timely rescued during remyelination and accelerated by the grafted neural precursors. Moreover, mouse and human iPSC‐derived oligodendrocytes express Cx47, which co‐labels with astrocyte Cx43, indicating their integration into the panglial network. These data suggest that in rodents, full lesion repair following transplantation occurs by panglial reconstruction in addition to remyelination. Targeting panglial elements by cell therapy or pharmacological compounds may help accelerating or stabilizing re/myelination in myelin disorders.

  • beneficial contribution of ipsc progeny to Connexin 47 dynamics during demyelination remyelination
    bioRxiv, 2020
    Co-Authors: Sabah Mozafari, Cyrille Deboux, Cecilia Laterza, Marc Ehrlich, Tanja Kuhlmann, Gianvito Martino, Anne Baronvan Evercooren
    Abstract:

    Abstract Oligodendrocytes are extensively coupled to astrocytes, a phenomenon ensuring glial homeostasis and maintenance of CNS myelin. Molecular disruption of this communication occurs in demyelinating diseases such as multiple sclerosis. Less is known about the vulnerability and reconstruction of the panglial network during adult demyelination-remyelination. Here, we took advantage of LPC-induced demyelination to investigate the expression dynamics of the oligodendrocyte specific Connexin 47 (Cx47) and whether this dynamic could be modulated by grafted iPSC-neural progeny. Our data show that deconstruction of the panglial network following demyelination is larger in size than demyelination. Loss of Cx47 expression is timely rescued during remyelination and accelerated by the grafted neural precursors. Moreover, mouse and human iPS-derived oligodendrocytes express Cx47, which co-labels with astrocyte Cx43, indicating their integration into the panglial network. These data suggest that full lesion repair following transplantation occurs by panglial reconstruction in addition to remyelination. Targeting panglial elements by cell therapy or pharmacological compounds may help accelerating or stabilizing re/myelination in myelin disorders.

Marc Ehrlich - One of the best experts on this subject based on the ideXlab platform.

  • Beneficial contribution of induced pluripotent stem cell-progeny to Connexin 47 dynamics during demyelination-remyelination
    Glia, 2020
    Co-Authors: Sabah Mozafari, Cyrille Deboux, Cecilia Laterza, Marc Ehrlich, Tanja Kuhlmann, Gianvito Martino, Anne Baron-van Evercooren
    Abstract:

    Oligodendrocytes are extensively coupled to astrocytes, a phenomenon ensuring glial homeostasis and maintenance of central nervous system myelin. Molecular disruption of this communication occurs in demyelinating diseases such as multiple sclerosis. Less is known about the vulnerability and reconstruction of the panglial network during adult demyelination‐remyelination. Here, we took advantage of lysolcithin‐induced demyelination to investigate the expression dynamics of the oligodendrocyte specific Connexin 47 (Cx47) and to some extent that of astrocyte Cx43, and whether this dynamic could be modulated by grafted induced pluripotent stem cell (iPSC)‐neural progeny. Our data show that disruption of Cx43‐Cx47 mediated hetero‐cellular gap‐junction intercellular communication following demyelination is larger in size than demyelination. Loss of Cx47 expression is timely rescued during remyelination and accelerated by the grafted neural precursors. Moreover, mouse and human iPSC‐derived oligodendrocytes express Cx47, which co‐labels with astrocyte Cx43, indicating their integration into the panglial network. These data suggest that in rodents, full lesion repair following transplantation occurs by panglial reconstruction in addition to remyelination. Targeting panglial elements by cell therapy or pharmacological compounds may help accelerating or stabilizing re/myelination in myelin disorders.

  • beneficial contribution of ipsc progeny to Connexin 47 dynamics during demyelination remyelination
    bioRxiv, 2020
    Co-Authors: Sabah Mozafari, Cyrille Deboux, Cecilia Laterza, Marc Ehrlich, Tanja Kuhlmann, Gianvito Martino, Anne Baronvan Evercooren
    Abstract:

    Abstract Oligodendrocytes are extensively coupled to astrocytes, a phenomenon ensuring glial homeostasis and maintenance of CNS myelin. Molecular disruption of this communication occurs in demyelinating diseases such as multiple sclerosis. Less is known about the vulnerability and reconstruction of the panglial network during adult demyelination-remyelination. Here, we took advantage of LPC-induced demyelination to investigate the expression dynamics of the oligodendrocyte specific Connexin 47 (Cx47) and whether this dynamic could be modulated by grafted iPSC-neural progeny. Our data show that deconstruction of the panglial network following demyelination is larger in size than demyelination. Loss of Cx47 expression is timely rescued during remyelination and accelerated by the grafted neural precursors. Moreover, mouse and human iPS-derived oligodendrocytes express Cx47, which co-labels with astrocyte Cx43, indicating their integration into the panglial network. These data suggest that full lesion repair following transplantation occurs by panglial reconstruction in addition to remyelination. Targeting panglial elements by cell therapy or pharmacological compounds may help accelerating or stabilizing re/myelination in myelin disorders.