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The effects of postmortem delay on mouse and human microglia gene expression
Yang Heng1, Marissa L Dubbelaar1, Suely K N Marie2
1Department of Biomedical Sciences of Cells & Systems, Section Molecular Neurobiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Glia
|December 9, 2020
Summary
Postmortem delay (PMD) has minimal impact on mouse microglia gene expression, affecting only 50 genes. These subtle changes, related to mitochondrial and ribosomal functions, were also observed in human microglia transcriptomes, necessitating careful consideration in research.
Area of Science:
- Neuroscience
- Immunology
- Genomics
Background:
- Microglia are key immune cells in the central nervous system (CNS).
- Transcriptional profiling of microglia has advanced understanding of their functions.
- Human CNS sample analysis is complicated by potential pathology and postmortem delay (PMD).
Purpose of the Study:
- To investigate the impact of postmortem delay (PMD) on the microglia transcriptome.
- To identify specific genes affected by PMD in both mouse and human microglia.
- To provide a reference set of PMD-affected genes for future transcriptomic analyses.
Main Methods:
- Microglia were isolated from mice using fluorescence-activated cell sorting (FACS) after varying PMDs (0-24 hours).
- RNA quality and gene expression profiles were analyzed.
- Mouse microglia gene expression data was compared with previously generated human microglia transcriptomes.
Main Results:
- Microglia viability decreased with increasing PMD, but high-quality RNA was obtainable up to 12 hours.
- PMD had a limited effect on mouse microglia gene expression, with only 50 differentially expressed genes identified.
- These 50 genes were primarily associated with mitochondrial, ribosomal, and protein binding functions.
- A subset of these genes (31) had human homologs and showed similar PMD-related expression changes in human microglia.
Conclusions:
- Postmortem delay induces subtle but detectable changes in microglia gene expression.
- A specific set of genes sensitive to PMD has been identified in both mouse and human microglia.
- Researchers must account for PMD when analyzing microglia transcriptomes to ensure accurate interpretation of results.

