Single-cell mass cytometry reveals complex myeloid cell composition in active lesions of progressive multiple sclerosis

Chotima Böttcher; Marlijn van der Poel; Camila Fernández-Zapata; Stephan Schlickeiser; Julia K H Leman; Cheng-Chih Hsiao; Mark R Mizee; null Adelia; Maria C J Vincenten; Desiree Kunkel; Inge Huitinga; Jörg Hamann; Josef Priller

doi:10.1186/s40478-020-01010-8

Single-cell mass cytometry reveals complex myeloid cell composition in active lesions of progressive multiple sclerosis

Chotima Böttcher, Marlijn van der Poel, Camila Fernández-Zapata, Stephan Schlickeiser, Julia K H Leman, Cheng-Chih Hsiao, Mark R Mizee, Adelia, Maria C J Vincenten, Desiree Kunkel, Inge Huitinga, Jörg Hamann, Josef Priller

Netherlands Institute for Neuroscience (NIN)

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Abstract

Myeloid cells contribute to inflammation and demyelination in the early stages of multiple sclerosis (MS), but it is still unclear to what extent these cells are involved in active lesion formation in progressive MS (PMS). Here, we have harnessed the power of single-cell mass cytometry (CyTOF) to compare myeloid cell phenotypes in active lesions of PMS donors with those in normal-appearing white matter from the same donors and control white matter from non-MS donors. CyTOF measurements of a total of 74 targeted proteins revealed a decreased abundance of homeostatic and TNFhi microglia, and an increase in highly phagocytic and activated microglia states in active lesions of PMS donors. Interestingly, in contrast to results obtained from studies of the inflammatory early disease stages of MS, infiltrating monocyte-derived macrophages were scarce in active lesions of PMS, suggesting fundamental differences of myeloid cell composition in advanced stages of PMS.

Original language	English
Pages (from-to)	136
Journal	Acta neuropathologica communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1186/s40478-020-01010-8
Publication status	Published - 2020

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Böttcher, C., van der Poel, M., Fernández-Zapata, C., Schlickeiser, S., Leman, J. K. H., Hsiao, C.-C., Mizee, M. R., Adelia, Vincenten, M. C. J., Kunkel, D., Huitinga, I., Hamann, J., & Priller, J. (2020). Single-cell mass cytometry reveals complex myeloid cell composition in active lesions of progressive multiple sclerosis. Acta neuropathologica communications, 8(1), 136. https://doi.org/10.1186/s40478-020-01010-8

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title = "Single-cell mass cytometry reveals complex myeloid cell composition in active lesions of progressive multiple sclerosis",

abstract = "Myeloid cells contribute to inflammation and demyelination in the early stages of multiple sclerosis (MS), but it is still unclear to what extent these cells are involved in active lesion formation in progressive MS (PMS). Here, we have harnessed the power of single-cell mass cytometry (CyTOF) to compare myeloid cell phenotypes in active lesions of PMS donors with those in normal-appearing white matter from the same donors and control white matter from non-MS donors. CyTOF measurements of a total of 74 targeted proteins revealed a decreased abundance of homeostatic and TNFhi microglia, and an increase in highly phagocytic and activated microglia states in active lesions of PMS donors. Interestingly, in contrast to results obtained from studies of the inflammatory early disease stages of MS, infiltrating monocyte-derived macrophages were scarce in active lesions of PMS, suggesting fundamental differences of myeloid cell composition in advanced stages of PMS.",

author = "Chotima B{\"o}ttcher and {van der Poel}, Marlijn and Camila Fern{\'a}ndez-Zapata and Stephan Schlickeiser and Leman, {Julia K H} and Cheng-Chih Hsiao and Mizee, {Mark R} and Adelia and Vincenten, {Maria C J} and Desiree Kunkel and Inge Huitinga and J{\"o}rg Hamann and Josef Priller",

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Böttcher, C, van der Poel, M, Fernández-Zapata, C, Schlickeiser, S, Leman, JKH, Hsiao, C-C, Mizee, MR, Adelia, Vincenten, MCJ, Kunkel, D, Huitinga, I , Hamann, J & Priller, J 2020, 'Single-cell mass cytometry reveals complex myeloid cell composition in active lesions of progressive multiple sclerosis', Acta neuropathologica communications, vol. 8, no. 1, pp. 136. https://doi.org/10.1186/s40478-020-01010-8

TY - JOUR

T1 - Single-cell mass cytometry reveals complex myeloid cell composition in active lesions of progressive multiple sclerosis

AU - Böttcher, Chotima

AU - van der Poel, Marlijn

AU - Fernández-Zapata, Camila

AU - Schlickeiser, Stephan

AU - Leman, Julia K H

AU - Hsiao, Cheng-Chih

AU - Mizee, Mark R

AU - Adelia, null

AU - Vincenten, Maria C J

AU - Kunkel, Desiree

AU - Huitinga, Inge

AU - Hamann, Jörg

AU - Priller, Josef

PY - 2020

Y1 - 2020

N2 - Myeloid cells contribute to inflammation and demyelination in the early stages of multiple sclerosis (MS), but it is still unclear to what extent these cells are involved in active lesion formation in progressive MS (PMS). Here, we have harnessed the power of single-cell mass cytometry (CyTOF) to compare myeloid cell phenotypes in active lesions of PMS donors with those in normal-appearing white matter from the same donors and control white matter from non-MS donors. CyTOF measurements of a total of 74 targeted proteins revealed a decreased abundance of homeostatic and TNFhi microglia, and an increase in highly phagocytic and activated microglia states in active lesions of PMS donors. Interestingly, in contrast to results obtained from studies of the inflammatory early disease stages of MS, infiltrating monocyte-derived macrophages were scarce in active lesions of PMS, suggesting fundamental differences of myeloid cell composition in advanced stages of PMS.

AB - Myeloid cells contribute to inflammation and demyelination in the early stages of multiple sclerosis (MS), but it is still unclear to what extent these cells are involved in active lesion formation in progressive MS (PMS). Here, we have harnessed the power of single-cell mass cytometry (CyTOF) to compare myeloid cell phenotypes in active lesions of PMS donors with those in normal-appearing white matter from the same donors and control white matter from non-MS donors. CyTOF measurements of a total of 74 targeted proteins revealed a decreased abundance of homeostatic and TNFhi microglia, and an increase in highly phagocytic and activated microglia states in active lesions of PMS donors. Interestingly, in contrast to results obtained from studies of the inflammatory early disease stages of MS, infiltrating monocyte-derived macrophages were scarce in active lesions of PMS, suggesting fundamental differences of myeloid cell composition in advanced stages of PMS.

U2 - 10.1186/s40478-020-01010-8

DO - 10.1186/s40478-020-01010-8

M3 - Article

C2 - 32811567

SN - 2051-5960

VL - 8

SP - 136

JO - Acta neuropathologica communications

JF - Acta neuropathologica communications

IS - 1

ER -

Single-cell mass cytometry reveals complex myeloid cell composition in active lesions of progressive multiple sclerosis

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