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

被引:496
作者
Galatro, Thais F. [1 ,2 ]
Holtman, Inge R. [1 ]
Lerario, Antonio M. [3 ]
Vainchtein, Ilia D. [1 ]
Brouwer, Nieske [1 ]
Sola, Paula R. [2 ]
Veras, Mariana M. [4 ]
Pereira, Tulio F. [5 ,6 ]
Leite, Renata E. P. [4 ]
Moller, Thomas [7 ]
Wes, Paul D. [7 ]
Sogayar, Mari C. [5 ]
Laman, Jon D. [1 ]
den Dunnen, Wilfred [8 ]
Pasqualucci, Carlos A. [4 ]
Oba-Shinjo, Sueli M. [2 ]
Boddeke, Erik W. G. M. [1 ]
Marie, Suely K. N. [2 ,5 ]
Eggen, Bart J. L. [1 ]
机构
[1] Univ Groningen, Univ Med Ctr Groningen, Sect Med Physiol, Dept Neurosci, Groningen, Netherlands
[2] Univ Sao Paulo, Sch Med, Lab Mol & Cellular Biol, Dept Neurol, Sao Paulo, Brazil
[3] Univ Michigan, Div Metab Endocrinol & Diabet, Dept Internal Med, Ann Arbor, MI 48109 USA
[4] Univ Sao Paulo, Sch Med, Brazilian Aging Brain Study Grp, Sao Paulo, Brazil
[5] Univ Sao Paulo, Ctr Studies Cellular & Mol Therapy NAP NETCEM NUC, Sao Paulo, Brazil
[6] Univ Sao Paulo, Chem Inst, Dept Biochem, Sao Paulo, Brazil
[7] Lundbeck Res USA, Neuroinflammat Dis Biol Unit, Paramus, NJ USA
[8] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol, Groningen, Netherlands
基金
巴西圣保罗研究基金会;
关键词
GENE-EXPRESSION SIGNATURE; ADULT-MOUSE; HUMAN BRAIN; CELLS; REGULATOR; RECEPTOR; DISEASE; CNS; PROLIFERATION; ASTROCYTES;
D O I
10.1038/nn.4597
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:1162 / +
页数:12
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