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Series GSE99074 Query DataSets for GSE99074
Status Public on May 19, 2017
Title Transcriptomic analysis of purified human cortical microglia reveals age-associated changes
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Purpose: Microglia are essential for central nervous system (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. We identified an age-associated gene signature in human microglia that was enriched for genes involved in cell adhesion, axonal guidance, cell surface receptor expression, and actin disassembly.
Methods: mRNA profiles of 39 human microglia samples isolated from subjects with intact cognition, 16 corresponding superior parietal cortex tissue and 10 epilepsy surgical samples were generated in a Illumina HiSEQ 2500 sequencer. mRNA profiles of 6 parietal cortex from mice were prepared with a Quantseq 3’mRNA-Seq kit (Lexogen, USA). Reads were aligned to the hg38 assembly of the human genome using STAR and quantified at the gene level by featureCounts. Differential expression between whole brain tissue, surgical samples and isolated microglia was assessed with limma.
Results: Overall, genes expressed by human microglia are similar to those in mouse, including established microglia genes CX3CR1, P2YR12, 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, Fc-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.
Conclusions: Here we present the an extensive human microglia gene expression profile. Critical differences with mouse microglia, especially in the context of aging, were observed which highlight the necessity to independently study human microglia. These data and analyses serve as a starting point to address human-specific microglia genes and functions under physiological and neuropathological conditions.
 
Overall design mRNA profiles of 39 human microglia samples isolated from subjects with intact cognition, 16 corresponding superior parietal cortex tissue and 10 epilepsy surgical samples were generated in a Illumina HiSEQ 2500 sequencer. mRNA profiles of 6 parietal cortex from mice were prepared with a Quantseq 3’mRNA-Seq kit (Lexogen, USA).
 
Contributor(s) Galatro TF, Holtman IR, Lerario AM, Vainchtein ID, Brower N, Sola P, Veras M, Pereira T, Leite R, Möller T, Wes PD, Sogayar MC, Laman JD, denDunnen W, Pasqualucci CA, Oba-Shinjo SM, Boddeke EW, Marie SN, Eggen BJ
Citation(s) 28671693
Submission date May 18, 2017
Last update date Mar 27, 2019
Contact name Antonio Marcondes Lerario
E-mail(s) alerario@umich.edu
Phone 7347737640
Organization name University of Michigan
Department MEND
Lab Hammer Lab
Street address 109 Zina Pitcher Place, 1528 BSRB
City Ann Arbor
State/province MI
ZIP/Postal code 48109
Country USA
 
Platforms (2)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (71)
GSM3081106 spm09
GSM3081107 spm08
GSM3081108 spm06
Relations
BioProject PRJNA387182
SRA SRP107337

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MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE99074_HumanMicrogliaBrainCounts.txt.gz 2.4 Mb (ftp)(http) TXT
GSE99074_HumanMicrogliaBrainVoomNormalization.txt.gz 11.1 Mb (ftp)(http) TXT
GSE99074_MouseBrainCounts.txt.gz 176.9 Kb (ftp)(http) TXT
GSE99074_MouseBrainVoomNormalization.txt.gz 449.7 Kb (ftp)(http) TXT
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