Transcriptomic analysis of purified human cortical microglia reveals age-associated changes

Thais F Galatro; Inge R Holtman; Antonio M Lerario; Ilia D Vainchtein; Nieske Brouwer; Paula R Sola; Mariana M Veras; Tulio F Pereira; Renata E P Leite; Thomas Möller; Paul D Wes; Mari C Sogayar; Jon D Laman; Wilfred den Dunnen; Carlos A Pasqualucci; Sueli M Oba-Shinjo; Erik W G M Boddeke; Suely K N Marie; Bart J L Eggen

doi:10.1038/nn.4597

Transcriptomic analysis of purified human cortical microglia reveals age-associated changes

Thais F Galatro, Inge R Holtman, Antonio M Lerario, Ilia D Vainchtein, Nieske Brouwer, Paula R Sola, Mariana M Veras, Tulio F Pereira, Renata E P Leite, Thomas Möller, Paul D Wes, Mari C Sogayar, Jon D Laman, Wilfred den Dunnen, Carlos A Pasqualucci, Sueli M Oba-Shinjo, Erik W G M Boddeke, Suely K N Marie, Bart J L Eggen

Translational Immunology Groningen (TRIGR)

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Abstract

Microglia are essential for CNS homeostasis and innate neuroimmune function, and play important roles in neurodegeneration and brain aging. Here we present gene expression profiles of purified microglia isolated at autopsy from the parietal cortex of 39 human subjects with intact cognition. Overall, genes expressed by human microglia were similar to those in mouse, including established microglial genes CX3CR1, P2RY12 and ITGAM (CD11B). However, a number of immune genes, not identified as part of the mouse microglial signature, were abundantly expressed in human microglia, including TLR, F-c gamma and SIGLEC receptors, as well as TAL1 and IFI16, regulators of proliferation and cell cycle. Age-associated changes in human microglia were enriched for genes involved in cell adhesion, axonal guidance, cell surface receptor expression and actin (dis)assembly. Limited overlap was observed in microglial genes regulated during aging between mice and humans, indicating that human and mouse microglia age differently.

Original language	English
Pages (from-to)	1162-1171
Number of pages	10
Journal	Nature neuroscience
Volume	20
Issue number	8
DOIs	https://doi.org/10.1038/nn.4597
Publication status	Published - Aug-2017

Keywords

GENE-EXPRESSION SIGNATURE
ADULT-MOUSE
HUMAN BRAIN
CELLS
REGULATOR
RECEPTOR
DISEASE
CNS
PROLIFERATION
ASTROCYTES

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Galatro, T. F., Holtman, I. R., Lerario, A. M., Vainchtein, I. D., Brouwer, N., Sola, P. R., Veras, M. M., Pereira, T. F., Leite, R. E. P., Möller, T., Wes, P. D., Sogayar, M. C., Laman, J. D., den Dunnen, W., Pasqualucci, C. A., Oba-Shinjo, S. M., Boddeke, E. W. G. M., Marie, S. K. N., & Eggen, B. J. L. (2017). Transcriptomic analysis of purified human cortical microglia reveals age-associated changes. Nature neuroscience, 20(8), 1162-1171. https://doi.org/10.1038/nn.4597

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title = "Transcriptomic analysis of purified human cortical microglia reveals age-associated changes",

abstract = "Microglia are essential for CNS homeostasis and innate neuroimmune function, and play important roles in neurodegeneration and brain aging. Here we present gene expression profiles of purified microglia isolated at autopsy from the parietal cortex of 39 human subjects with intact cognition. Overall, genes expressed by human microglia were similar to those in mouse, including established microglial genes CX3CR1, P2RY12 and ITGAM (CD11B). However, a number of immune genes, not identified as part of the mouse microglial signature, were abundantly expressed in human microglia, including TLR, F-c gamma and SIGLEC receptors, as well as TAL1 and IFI16, regulators of proliferation and cell cycle. Age-associated changes in human microglia were enriched for genes involved in cell adhesion, axonal guidance, cell surface receptor expression and actin (dis)assembly. Limited overlap was observed in microglial genes regulated during aging between mice and humans, indicating that human and mouse microglia age differently.",

keywords = "GENE-EXPRESSION SIGNATURE, ADULT-MOUSE, HUMAN BRAIN, CELLS, REGULATOR, RECEPTOR, DISEASE, CNS, PROLIFERATION, ASTROCYTES",

author = "Galatro, {Thais F} and Holtman, {Inge R} and Lerario, {Antonio M} and Vainchtein, {Ilia D} and Nieske Brouwer and Sola, {Paula R} and Veras, {Mariana M} and Pereira, {Tulio F} and Leite, {Renata E P} and Thomas M{\"o}ller and Wes, {Paul D} and Sogayar, {Mari C} and Laman, {Jon D} and {den Dunnen}, Wilfred and Pasqualucci, {Carlos A} and Oba-Shinjo, {Sueli M} and Boddeke, {Erik W G M} and Marie, {Suely K N} and Eggen, {Bart J L}",

year = "2017",

month = aug,

doi = "10.1038/nn.4597",

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volume = "20",

pages = "1162--1171",

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Galatro, TF, Holtman, IR, Lerario, AM, Vainchtein, ID, Brouwer, N, Sola, PR, Veras, MM, Pereira, TF, Leite, REP, Möller, T, Wes, PD, Sogayar, MC, Laman, JD , den Dunnen, W, Pasqualucci, CA, Oba-Shinjo, SM, Boddeke, EWGM, Marie, SKN & Eggen, BJL 2017, 'Transcriptomic analysis of purified human cortical microglia reveals age-associated changes', Nature neuroscience, vol. 20, no. 8, pp. 1162-1171. https://doi.org/10.1038/nn.4597

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T1 - Transcriptomic analysis of purified human cortical microglia reveals age-associated changes

AU - Galatro, Thais F

AU - Holtman, Inge R

AU - Lerario, Antonio M

AU - Vainchtein, Ilia D

AU - Brouwer, Nieske

AU - Sola, Paula R

AU - Veras, Mariana M

AU - Pereira, Tulio F

AU - Leite, Renata E P

AU - Möller, Thomas

AU - Wes, Paul D

AU - Sogayar, Mari C

AU - Laman, Jon D

AU - den Dunnen, Wilfred

AU - Pasqualucci, Carlos A

AU - Oba-Shinjo, Sueli M

AU - Boddeke, Erik W G M

AU - Marie, Suely K N

AU - Eggen, Bart J L

PY - 2017/8

Y1 - 2017/8

N2 - Microglia are essential for CNS homeostasis and innate neuroimmune function, and play important roles in neurodegeneration and brain aging. Here we present gene expression profiles of purified microglia isolated at autopsy from the parietal cortex of 39 human subjects with intact cognition. Overall, genes expressed by human microglia were similar to those in mouse, including established microglial genes CX3CR1, P2RY12 and ITGAM (CD11B). However, a number of immune genes, not identified as part of the mouse microglial signature, were abundantly expressed in human microglia, including TLR, F-c gamma and SIGLEC receptors, as well as TAL1 and IFI16, regulators of proliferation and cell cycle. Age-associated changes in human microglia were enriched for genes involved in cell adhesion, axonal guidance, cell surface receptor expression and actin (dis)assembly. Limited overlap was observed in microglial genes regulated during aging between mice and humans, indicating that human and mouse microglia age differently.

AB - Microglia are essential for CNS homeostasis and innate neuroimmune function, and play important roles in neurodegeneration and brain aging. Here we present gene expression profiles of purified microglia isolated at autopsy from the parietal cortex of 39 human subjects with intact cognition. Overall, genes expressed by human microglia were similar to those in mouse, including established microglial genes CX3CR1, P2RY12 and ITGAM (CD11B). However, a number of immune genes, not identified as part of the mouse microglial signature, were abundantly expressed in human microglia, including TLR, F-c gamma and SIGLEC receptors, as well as TAL1 and IFI16, regulators of proliferation and cell cycle. Age-associated changes in human microglia were enriched for genes involved in cell adhesion, axonal guidance, cell surface receptor expression and actin (dis)assembly. Limited overlap was observed in microglial genes regulated during aging between mice and humans, indicating that human and mouse microglia age differently.

KW - GENE-EXPRESSION SIGNATURE

KW - ADULT-MOUSE

KW - HUMAN BRAIN

KW - CELLS

KW - REGULATOR

KW - RECEPTOR

KW - DISEASE

KW - CNS

KW - PROLIFERATION

KW - ASTROCYTES

U2 - 10.1038/nn.4597

DO - 10.1038/nn.4597

M3 - Article

C2 - 28671693

SN - 1097-6256

VL - 20

SP - 1162

EP - 1171

JO - Nature neuroscience

JF - Nature neuroscience

IS - 8

ER -

Transcriptomic analysis of purified human cortical microglia reveals age-associated changes

Abstract

Keywords

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