Nat Genet: A transcriptional map of microglia related to the central nervous system

Microglia are the tissue-resident macrophages of the central nervous system (CNS), which play a vital role in the shearing of synapses, neuronal plasticity, and the maintenance of local immune surveillance in the brain .

Past disease studies have shown that microglia dysfunction is closely related to many neurological diseases , but these highly plastic cells have not been studied at the population level.
So far, research on microglia gene expression has been limited to relatively small samples of frozen post-death tissues from existing brain banks or fresh surgical samples from restricted patient populations, usually due toPatients with epilepsy or surrounding tissues undergoing temporal lobectomy.

Single-cell transcriptomics studies of these samples indicate that the function of microglia may vary depending on age, gender, and brain region.
Therefore, it is usually impossible to get similar conclusions in the same scale of research.

In this study, the researchers aimed to conduct a population-scale study of microglia to understand how age, gender, pathology, cortical anatomy, and common germline genetic variations affect the transcriptome of microglia.

Schematic diagram of research design

The researchers mainly analyzed the gene expression variation of primary microglia isolated from 141 patients undergoing neurosurgery.
Through single-cell sequencing and batch RNA sequencing, and using expression quantitative trait locus (eQTL) mapping to determine how age, gender, and clinical pathology affect microglia gene expression and which genetic variants have microglia-specific functions.

By human induced pluripotent based on stem cells (iPS) macrophages model, the researchers BIN1 fine mapping the candidate locus mutations associated with Alzheimer's disease.

Transcriptional heterogeneity of microglia

All in all, the results of this study reveal a population-scale transcriptional map of microglia, which is essential for the development and disease of the human central nervous system.

Original source:

Young, AMH, Kumasaka, N.