Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry

Chotima Böttcher; Stephan Schlickeiser; Marjolein A. M. Sneeboer; Desiree Kunkel; Anniki Knop; Evdokia Paza; Pawel Fidzinski; Larissa Kraus; Gijsje J. L. Snijders; René S Kahn; Axel R Schulz; Henrik E Mei; Elly M. Hol; Britta Siegmund; Rainer Glauben; Eike J Spruth; Lot D De Witte; Josef Priller

doi:10.1038/s41593-018-0290-2

Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry

Chotima Böttcher, Stephan Schlickeiser, Marjolein A. M. Sneeboer, Desiree Kunkel, Anniki Knop, Evdokia Paza, Pawel Fidzinski, Larissa Kraus, Gijsje J. L. Snijders, René S Kahn, Axel R Schulz, Henrik E Mei, Elly M. Hol, Britta Siegmund, Rainer Glauben, Eike J Spruth, Lot D De Witte, Josef Priller

Research output: Contribution to journal › Article › peer-review

Abstract

Microglia, the specialized innate immune cells of the CNS, play crucial roles in neural development and function. Different phenotypes and functions have been ascribed to rodent microglia, but little is known about human microglia (huMG) heterogeneity. Difficulties in procuring huMG and their susceptibility to cryopreservation damage have limited large-scale studies. Here we applied multiplexed mass cytometry for a comprehensive characterization of postmortem huMG (10³ – 10⁴ cells). We determined expression levels of 57 markers on huMG isolated from up to five different brain regions of nine donors. We identified the phenotypic signature of huMG, which was distinct from peripheral myeloid cells but was comparable to fresh huMG. We detected microglia regional heterogeneity using a hybrid workflow combining Cytobank and R/Bioconductor for multidimensional data analysis. Together, these methodologies allowed us to perform high-dimensional, large-scale immunophenotyping of huMG at the single-cell level, which facilitates their unambiguous profiling in health and disease.

Original language	English
Pages (from-to)	78-90
Number of pages	13
Journal	Nature Neuroscience
Volume	22
Issue number	1
Early online date	17 Dec 2018
DOIs	https://doi.org/10.1038/s41593-018-0290-2
Publication status	Published - 31 Jan 2019

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Josef Priller
- Deanery of Clinical Sciences - Chair of Brain Inflammation and Repair
- Centre for Clinical Brain Sciences
- Edinburgh Neuroscience
- Euan MacDonald Centre for Motor Neurone Disease Research
Person: Academic: Research Active

Cite this

Böttcher, C., Schlickeiser, S., Sneeboer, M. A. M., Kunkel, D., Knop, A., Paza, E., Fidzinski, P., Kraus, L., Snijders, G. J. L., Kahn, R. S., Schulz, A. R., Mei, H. E., Hol, E. M., Siegmund, B., Glauben, R., Spruth, E. J., De Witte, L. D., & Priller, J. (2019). Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry. Nature Neuroscience, 22(1), 78-90. https://doi.org/10.1038/s41593-018-0290-2

Böttcher, Chotima ; Schlickeiser, Stephan ; Sneeboer, Marjolein A. M. ; Kunkel, Desiree ; Knop, Anniki ; Paza, Evdokia ; Fidzinski, Pawel ; Kraus, Larissa ; Snijders, Gijsje J. L. ; Kahn, René S ; Schulz, Axel R ; Mei, Henrik E ; Hol, Elly M. ; Siegmund, Britta ; Glauben, Rainer ; Spruth, Eike J ; De Witte, Lot D ; Priller, Josef. / Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry. In: Nature Neuroscience. 2019 ; Vol. 22, No. 1. pp. 78-90.

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abstract = "Microglia, the specialized innate immune cells of the CNS, play crucial roles in neural development and function. Different phenotypes and functions have been ascribed to rodent microglia, but little is known about human microglia (huMG) heterogeneity. Difficulties in procuring huMG and their susceptibility to cryopreservation damage have limited large-scale studies. Here we applied multiplexed mass cytometry for a comprehensive characterization of postmortem huMG (103 – 104 cells). We determined expression levels of 57 markers on huMG isolated from up to five different brain regions of nine donors. We identified the phenotypic signature of huMG, which was distinct from peripheral myeloid cells but was comparable to fresh huMG. We detected microglia regional heterogeneity using a hybrid workflow combining Cytobank and R/Bioconductor for multidimensional data analysis. Together, these methodologies allowed us to perform high-dimensional, large-scale immunophenotyping of huMG at the single-cell level, which facilitates their unambiguous profiling in health and disease.",

author = "Chotima B{\"o}ttcher and Stephan Schlickeiser and Sneeboer, {Marjolein A. M.} and Desiree Kunkel and Anniki Knop and Evdokia Paza and Pawel Fidzinski and Larissa Kraus and Snijders, {Gijsje J. L.} and Kahn, {Ren{\'e} S} and Schulz, {Axel R} and Mei, {Henrik E} and Hol, {Elly M.} and Britta Siegmund and Rainer Glauben and Spruth, {Eike J} and {De Witte}, {Lot D} and Josef Priller",

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Böttcher, C, Schlickeiser, S, Sneeboer, MAM, Kunkel, D, Knop, A, Paza, E, Fidzinski, P, Kraus, L, Snijders, GJL, Kahn, RS, Schulz, AR, Mei, HE, Hol, EM, Siegmund, B, Glauben, R, Spruth, EJ, De Witte, LD & Priller, J 2019, 'Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry', Nature Neuroscience, vol. 22, no. 1, pp. 78-90. https://doi.org/10.1038/s41593-018-0290-2

Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry. / Böttcher, Chotima; Schlickeiser, Stephan; Sneeboer, Marjolein A. M.; Kunkel, Desiree; Knop, Anniki; Paza, Evdokia; Fidzinski, Pawel; Kraus, Larissa; Snijders, Gijsje J. L.; Kahn, René S; Schulz, Axel R; Mei, Henrik E; Hol, Elly M.; Siegmund, Britta; Glauben, Rainer; Spruth, Eike J; De Witte, Lot D; Priller, Josef.

In: Nature Neuroscience, Vol. 22, No. 1, 31.01.2019, p. 78-90.

Research output: Contribution to journal › Article › peer-review

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AU - Böttcher, Chotima

AU - Schlickeiser, Stephan

AU - Sneeboer, Marjolein A. M.

AU - Kunkel, Desiree

AU - Knop, Anniki

AU - Paza, Evdokia

AU - Fidzinski, Pawel

AU - Kraus, Larissa

AU - Snijders, Gijsje J. L.

AU - Kahn, René S

AU - Schulz, Axel R

AU - Mei, Henrik E

AU - Hol, Elly M.

AU - Siegmund, Britta

AU - Glauben, Rainer

AU - Spruth, Eike J

AU - De Witte, Lot D

AU - Priller, Josef

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AB - Microglia, the specialized innate immune cells of the CNS, play crucial roles in neural development and function. Different phenotypes and functions have been ascribed to rodent microglia, but little is known about human microglia (huMG) heterogeneity. Difficulties in procuring huMG and their susceptibility to cryopreservation damage have limited large-scale studies. Here we applied multiplexed mass cytometry for a comprehensive characterization of postmortem huMG (103 – 104 cells). We determined expression levels of 57 markers on huMG isolated from up to five different brain regions of nine donors. We identified the phenotypic signature of huMG, which was distinct from peripheral myeloid cells but was comparable to fresh huMG. We detected microglia regional heterogeneity using a hybrid workflow combining Cytobank and R/Bioconductor for multidimensional data analysis. Together, these methodologies allowed us to perform high-dimensional, large-scale immunophenotyping of huMG at the single-cell level, which facilitates their unambiguous profiling in health and disease.

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JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

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