Publication

Tissue Transglutaminase Promotes Early Differentiation of Oligodendrocyte Progenitor Cells

Pinzon, N. E., van Mierlo, H., de Jonge, J. C., Breve, J. J. P., Bol, J. G. J. M., Drukarch, B., van Dam, A-M. & Baron, W., 2-Jul-2019, In : Frontiers in cellular neuroscience. 13, 17 p., 281.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Pinzon, N. E., van Mierlo, H., de Jonge, J. C., Breve, J. J. P., Bol, J. G. J. M., Drukarch, B., ... Baron, W. (2019). Tissue Transglutaminase Promotes Early Differentiation of Oligodendrocyte Progenitor Cells. Frontiers in cellular neuroscience, 13, [281]. https://doi.org/10.3389/fncel.2019.00281

Author

Pinzon, Nathaly Espitia ; van Mierlo, Hanneke ; de Jonge, Jenny C. ; Breve, John J. P. ; Bol, John G. J. M. ; Drukarch, Benjamin ; van Dam, Anne-Marie ; Baron, Wia. / Tissue Transglutaminase Promotes Early Differentiation of Oligodendrocyte Progenitor Cells. In: Frontiers in cellular neuroscience. 2019 ; Vol. 13.

Harvard

Pinzon, NE, van Mierlo, H, de Jonge, JC, Breve, JJP, Bol, JGJM, Drukarch, B, van Dam, A-M & Baron, W 2019, 'Tissue Transglutaminase Promotes Early Differentiation of Oligodendrocyte Progenitor Cells', Frontiers in cellular neuroscience, vol. 13, 281. https://doi.org/10.3389/fncel.2019.00281

Standard

Tissue Transglutaminase Promotes Early Differentiation of Oligodendrocyte Progenitor Cells. / Pinzon, Nathaly Espitia; van Mierlo, Hanneke; de Jonge, Jenny C.; Breve, John J. P.; Bol, John G. J. M.; Drukarch, Benjamin; van Dam, Anne-Marie; Baron, Wia.

In: Frontiers in cellular neuroscience, Vol. 13, 281, 02.07.2019.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Pinzon NE, van Mierlo H, de Jonge JC, Breve JJP, Bol JGJM, Drukarch B et al. Tissue Transglutaminase Promotes Early Differentiation of Oligodendrocyte Progenitor Cells. Frontiers in cellular neuroscience. 2019 Jul 2;13. 281. https://doi.org/10.3389/fncel.2019.00281


BibTeX

@article{54d4f5f8b46e42928f303253c3cfffad,
title = "Tissue Transglutaminase Promotes Early Differentiation of Oligodendrocyte Progenitor Cells",
abstract = "Demyelinated lesions of the central nervous system are characteristic for multiple sclerosis (MS). Remyelination is not very effective, particular at later stages of the disease, which results in a chronic neurodegenerative character with worsening of symptoms. Previously, we have shown that the enzyme Tissue Transglutaminase (TG2) is downregulated upon differentiation of oligodendrocyte progenitor cells (OPCs) into myelin-forming oligodendrocytes and that TG2 knock-out mice lag behind in remyelination after cuprizone-induced demyelination. Here, we examined whether astrocytic or oligodendroglial TG2 affects OPCs in a cell-specific manner to modulate their differentiation, and therefore myelination. Our findings indicate that human TG2-expressing astrocytes did not modulate OPC differentiation and myelination. In contrast, persistent TG2 expression upon OPC maturation or exogenously added recombinant TG2 accelerated OPC differentiation and myelin membrane formation. Continuous exposure of recombinant TG2 to OPCs at different consecutive developmental stages, however, decreased OPC differentiation and myelin membrane formation, while it enhanced myelination in dorsal root ganglion neuron-OPC co-cultures. In MS lesions, TG2 is absent in OPCs, while human OPCs show TG2 immunoreactivity during brain development. Exposure to the MS-relevant pro-inflammatory cytokine IFN-gamma increased TG2 expression in OPCs and prolonged expression of endogenous TG2 upon differentiation. However, despite the increased TG2 levels, OPC maturation was not accelerated, indicating that TG2-mediated OPC differentiation may be counteracted by other pathways. Together, our data show that TG2, either endogenously expressed, or exogenously supplied to OPCs, accelerates early OPC differentiation. A better understanding of the role of TG2 in the OPC differentiation process during MS is of therapeutic interest to overcome remyelination failure.",
keywords = "tissue transglutaminase, oligodendrocyte progenitor cells, multiple sclerosis, remyelination, astrocytes, differentiation, MULTIPLE-SCLEROSIS LESIONS, MYELIN BASIC-PROTEIN, INTERFERON-GAMMA, REMYELINATION FAILURE, SIGNALING PATHWAY, PRECURSOR CELLS, NERVOUS-SYSTEM, SCHWANN-CELLS, RECRUITMENT, EXPRESSION",
author = "Pinzon, {Nathaly Espitia} and {van Mierlo}, Hanneke and {de Jonge}, {Jenny C.} and Breve, {John J. P.} and Bol, {John G. J. M.} and Benjamin Drukarch and {van Dam}, Anne-Marie and Wia Baron",
year = "2019",
month = "7",
day = "2",
doi = "10.3389/fncel.2019.00281",
language = "English",
volume = "13",
journal = "Frontiers in cellular neuroscience",
issn = "1662-5102",
publisher = "Frontiers Media SA",

}

RIS

TY - JOUR

T1 - Tissue Transglutaminase Promotes Early Differentiation of Oligodendrocyte Progenitor Cells

AU - Pinzon, Nathaly Espitia

AU - van Mierlo, Hanneke

AU - de Jonge, Jenny C.

AU - Breve, John J. P.

AU - Bol, John G. J. M.

AU - Drukarch, Benjamin

AU - van Dam, Anne-Marie

AU - Baron, Wia

PY - 2019/7/2

Y1 - 2019/7/2

N2 - Demyelinated lesions of the central nervous system are characteristic for multiple sclerosis (MS). Remyelination is not very effective, particular at later stages of the disease, which results in a chronic neurodegenerative character with worsening of symptoms. Previously, we have shown that the enzyme Tissue Transglutaminase (TG2) is downregulated upon differentiation of oligodendrocyte progenitor cells (OPCs) into myelin-forming oligodendrocytes and that TG2 knock-out mice lag behind in remyelination after cuprizone-induced demyelination. Here, we examined whether astrocytic or oligodendroglial TG2 affects OPCs in a cell-specific manner to modulate their differentiation, and therefore myelination. Our findings indicate that human TG2-expressing astrocytes did not modulate OPC differentiation and myelination. In contrast, persistent TG2 expression upon OPC maturation or exogenously added recombinant TG2 accelerated OPC differentiation and myelin membrane formation. Continuous exposure of recombinant TG2 to OPCs at different consecutive developmental stages, however, decreased OPC differentiation and myelin membrane formation, while it enhanced myelination in dorsal root ganglion neuron-OPC co-cultures. In MS lesions, TG2 is absent in OPCs, while human OPCs show TG2 immunoreactivity during brain development. Exposure to the MS-relevant pro-inflammatory cytokine IFN-gamma increased TG2 expression in OPCs and prolonged expression of endogenous TG2 upon differentiation. However, despite the increased TG2 levels, OPC maturation was not accelerated, indicating that TG2-mediated OPC differentiation may be counteracted by other pathways. Together, our data show that TG2, either endogenously expressed, or exogenously supplied to OPCs, accelerates early OPC differentiation. A better understanding of the role of TG2 in the OPC differentiation process during MS is of therapeutic interest to overcome remyelination failure.

AB - Demyelinated lesions of the central nervous system are characteristic for multiple sclerosis (MS). Remyelination is not very effective, particular at later stages of the disease, which results in a chronic neurodegenerative character with worsening of symptoms. Previously, we have shown that the enzyme Tissue Transglutaminase (TG2) is downregulated upon differentiation of oligodendrocyte progenitor cells (OPCs) into myelin-forming oligodendrocytes and that TG2 knock-out mice lag behind in remyelination after cuprizone-induced demyelination. Here, we examined whether astrocytic or oligodendroglial TG2 affects OPCs in a cell-specific manner to modulate their differentiation, and therefore myelination. Our findings indicate that human TG2-expressing astrocytes did not modulate OPC differentiation and myelination. In contrast, persistent TG2 expression upon OPC maturation or exogenously added recombinant TG2 accelerated OPC differentiation and myelin membrane formation. Continuous exposure of recombinant TG2 to OPCs at different consecutive developmental stages, however, decreased OPC differentiation and myelin membrane formation, while it enhanced myelination in dorsal root ganglion neuron-OPC co-cultures. In MS lesions, TG2 is absent in OPCs, while human OPCs show TG2 immunoreactivity during brain development. Exposure to the MS-relevant pro-inflammatory cytokine IFN-gamma increased TG2 expression in OPCs and prolonged expression of endogenous TG2 upon differentiation. However, despite the increased TG2 levels, OPC maturation was not accelerated, indicating that TG2-mediated OPC differentiation may be counteracted by other pathways. Together, our data show that TG2, either endogenously expressed, or exogenously supplied to OPCs, accelerates early OPC differentiation. A better understanding of the role of TG2 in the OPC differentiation process during MS is of therapeutic interest to overcome remyelination failure.

KW - tissue transglutaminase

KW - oligodendrocyte progenitor cells

KW - multiple sclerosis

KW - remyelination

KW - astrocytes

KW - differentiation

KW - MULTIPLE-SCLEROSIS LESIONS

KW - MYELIN BASIC-PROTEIN

KW - INTERFERON-GAMMA

KW - REMYELINATION FAILURE

KW - SIGNALING PATHWAY

KW - PRECURSOR CELLS

KW - NERVOUS-SYSTEM

KW - SCHWANN-CELLS

KW - RECRUITMENT

KW - EXPRESSION

U2 - 10.3389/fncel.2019.00281

DO - 10.3389/fncel.2019.00281

M3 - Article

C2 - 31312122

VL - 13

JO - Frontiers in cellular neuroscience

JF - Frontiers in cellular neuroscience

SN - 1662-5102

M1 - 281

ER -

ID: 91112869