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Neuronal vulnerability and multilineage diversity in multiple sclerosis

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Neuronal vulnerability and multilineage diversity in multiple sclerosis. / Schirmer, Lucas; Velmeshev, Dmitry; Holmqvist, Staffan; Kaufmann, Max; Werneburg, Sebastian; Jung, Diane; Vistnes, Stephanie; Stockley, John H; Young, Adam; Steindel, Maike; Tung, Brian; Goyal, Nitasha; Bhaduri, Aparna; Mayer, Simone; Engler, Jan Broder; Bayraktar, Omer A; Franklin, Robin J M; Haeussler, Maximilian; Reynolds, Richard; Schafer, Dorothy P; Friese, Manuel A; Shiow, Lawrence R; Kriegstein, Arnold R; Rowitch, David H.

in: NATURE, Jahrgang 573, Nr. 7772, 09.2019, S. 75-82.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Schirmer, L, Velmeshev, D, Holmqvist, S, Kaufmann, M, Werneburg, S, Jung, D, Vistnes, S, Stockley, JH, Young, A, Steindel, M, Tung, B, Goyal, N, Bhaduri, A, Mayer, S, Engler, JB, Bayraktar, OA, Franklin, RJM, Haeussler, M, Reynolds, R, Schafer, DP, Friese, MA, Shiow, LR, Kriegstein, AR & Rowitch, DH 2019, 'Neuronal vulnerability and multilineage diversity in multiple sclerosis', NATURE, Jg. 573, Nr. 7772, S. 75-82. https://doi.org/10.1038/s41586-019-1404-z

APA

Schirmer, L., Velmeshev, D., Holmqvist, S., Kaufmann, M., Werneburg, S., Jung, D., Vistnes, S., Stockley, J. H., Young, A., Steindel, M., Tung, B., Goyal, N., Bhaduri, A., Mayer, S., Engler, J. B., Bayraktar, O. A., Franklin, R. J. M., Haeussler, M., Reynolds, R., ... Rowitch, D. H. (2019). Neuronal vulnerability and multilineage diversity in multiple sclerosis. NATURE, 573(7772), 75-82. https://doi.org/10.1038/s41586-019-1404-z

Vancouver

Schirmer L, Velmeshev D, Holmqvist S, Kaufmann M, Werneburg S, Jung D et al. Neuronal vulnerability and multilineage diversity in multiple sclerosis. NATURE. 2019 Sep;573(7772):75-82. https://doi.org/10.1038/s41586-019-1404-z

Bibtex

@article{727e7f6dee2f4ee9a94c988dab5cce27,
title = "Neuronal vulnerability and multilineage diversity in multiple sclerosis",
abstract = "Multiple sclerosis (MS) is a neuroinflammatory disease with a relapsing-remitting disease course at early stages, distinct lesion characteristics in cortical grey versus subcortical white matter and neurodegeneration at chronic stages. Here we used single-nucleus RNA sequencing to assess changes in expression in multiple cell lineages in MS lesions and validated the results using multiplex in situ hybridization. We found selective vulnerability and loss of excitatory CUX2-expressing projection neurons in upper-cortical layers underlying meningeal inflammation; such MS neuron populations exhibited upregulation of stress pathway genes and long non-coding RNAs. Signatures of stressed oligodendrocytes, reactive astrocytes and activated microglia mapped most strongly to the rim of MS plaques. Notably, single-nucleus RNA sequencing identified phagocytosing microglia and/or macrophages by their ingestion and perinuclear import of myelin transcripts, confirmed by functional mouse and human culture assays. Our findings indicate lineage- and region-specific transcriptomic changes associated with selective cortical neuron damage and glial activation contributing to progression of MS lesions.",
author = "Lucas Schirmer and Dmitry Velmeshev and Staffan Holmqvist and Max Kaufmann and Sebastian Werneburg and Diane Jung and Stephanie Vistnes and Stockley, {John H} and Adam Young and Maike Steindel and Brian Tung and Nitasha Goyal and Aparna Bhaduri and Simone Mayer and Engler, {Jan Broder} and Bayraktar, {Omer A} and Franklin, {Robin J M} and Maximilian Haeussler and Richard Reynolds and Schafer, {Dorothy P} and Friese, {Manuel A} and Shiow, {Lawrence R} and Kriegstein, {Arnold R} and Rowitch, {David H}",
year = "2019",
month = sep,
doi = "10.1038/s41586-019-1404-z",
language = "English",
volume = "573",
pages = "75--82",
journal = "NATURE",
issn = "0028-0836",
publisher = "NATURE PUBLISHING GROUP",
number = "7772",

}

RIS

TY - JOUR

T1 - Neuronal vulnerability and multilineage diversity in multiple sclerosis

AU - Schirmer, Lucas

AU - Velmeshev, Dmitry

AU - Holmqvist, Staffan

AU - Kaufmann, Max

AU - Werneburg, Sebastian

AU - Jung, Diane

AU - Vistnes, Stephanie

AU - Stockley, John H

AU - Young, Adam

AU - Steindel, Maike

AU - Tung, Brian

AU - Goyal, Nitasha

AU - Bhaduri, Aparna

AU - Mayer, Simone

AU - Engler, Jan Broder

AU - Bayraktar, Omer A

AU - Franklin, Robin J M

AU - Haeussler, Maximilian

AU - Reynolds, Richard

AU - Schafer, Dorothy P

AU - Friese, Manuel A

AU - Shiow, Lawrence R

AU - Kriegstein, Arnold R

AU - Rowitch, David H

PY - 2019/9

Y1 - 2019/9

N2 - Multiple sclerosis (MS) is a neuroinflammatory disease with a relapsing-remitting disease course at early stages, distinct lesion characteristics in cortical grey versus subcortical white matter and neurodegeneration at chronic stages. Here we used single-nucleus RNA sequencing to assess changes in expression in multiple cell lineages in MS lesions and validated the results using multiplex in situ hybridization. We found selective vulnerability and loss of excitatory CUX2-expressing projection neurons in upper-cortical layers underlying meningeal inflammation; such MS neuron populations exhibited upregulation of stress pathway genes and long non-coding RNAs. Signatures of stressed oligodendrocytes, reactive astrocytes and activated microglia mapped most strongly to the rim of MS plaques. Notably, single-nucleus RNA sequencing identified phagocytosing microglia and/or macrophages by their ingestion and perinuclear import of myelin transcripts, confirmed by functional mouse and human culture assays. Our findings indicate lineage- and region-specific transcriptomic changes associated with selective cortical neuron damage and glial activation contributing to progression of MS lesions.

AB - Multiple sclerosis (MS) is a neuroinflammatory disease with a relapsing-remitting disease course at early stages, distinct lesion characteristics in cortical grey versus subcortical white matter and neurodegeneration at chronic stages. Here we used single-nucleus RNA sequencing to assess changes in expression in multiple cell lineages in MS lesions and validated the results using multiplex in situ hybridization. We found selective vulnerability and loss of excitatory CUX2-expressing projection neurons in upper-cortical layers underlying meningeal inflammation; such MS neuron populations exhibited upregulation of stress pathway genes and long non-coding RNAs. Signatures of stressed oligodendrocytes, reactive astrocytes and activated microglia mapped most strongly to the rim of MS plaques. Notably, single-nucleus RNA sequencing identified phagocytosing microglia and/or macrophages by their ingestion and perinuclear import of myelin transcripts, confirmed by functional mouse and human culture assays. Our findings indicate lineage- and region-specific transcriptomic changes associated with selective cortical neuron damage and glial activation contributing to progression of MS lesions.

U2 - 10.1038/s41586-019-1404-z

DO - 10.1038/s41586-019-1404-z

M3 - SCORING: Journal article

C2 - 31316211

VL - 573

SP - 75

EP - 82

JO - NATURE

JF - NATURE

SN - 0028-0836

IS - 7772

ER -