Microglia protect against age-associated brain pathologies - all scRNAseq datasets

Zipped cellranger_matrices file contains the filtered_feature_bc_matrices and the raw_feature_bc_matrices obtained from cellranger for the young (E...), middle-aged(S...), old (...vo...) and thalamic (TH...) datasets. The cellinfo csv files give the metadata for each cell kept in the analysis, with a relationship between each barcode and information such as the umi counts or the cell type annotation. The metadata file gives information about each sample, to trace back the sample names used in cellranger to the biological samples. On other tabs it also has qc information such as the thresholds used for each sample. The raw fastq files and RDS files are available at GEO: GSE267545 and GEO:GSE215440 with the same metadata as here as well as the SingleCellExperiment in form of RDS objects (with information such as normalised reads and dimensional reduction embedings) available at GEO: GSE267545 The code used to do the analysis is available in Anna-Williams GitHub and also in ZENODO: https://github.com/Anna-Williams/David-young (10.5281/zenodo.11199128) for the young dataset https://github.com/Anna-Williams/David-old (10.5281/zenodo.11199278) for the middle-aged dataset https://github.com/Anna-Williams/David-vold (10.5281/zenodo.11199322) for the old dataset https://github.com/Anna-Williams/David-Thalamus (10.5281/zenodo.11199349) for the thalamic dataset https://github.com/Anna-Williams/David-AgeIntegration (10.5281/zenodo.11199367) for the integration between the young, middle-aged and old datasets. Microglia are brain-resident macrophages that contribute to central nervous system development, maturation, and preservation. Here, we examine the consequences of lifelong absence of microglia on ageing using the Csf1rΔFIRE/ΔFIRE mouse model. In juvenile Csf1rΔFIRE/ΔFIRE mice, we show that microglia are largely dispensable for the transcriptomic maturation of other brain cell types. In contrast, with advancing age, multiple pathologies accumulate in Csf1rΔFIRE/ΔFIRE brains, astrocytes and oligodendrocyte-lineage cells become increasingly dysregulated, and white matter integrity declines, mimicking many of the pathological features of human CSF1R-related leukoencephalopathy. The thalamus is particularly sensitive to neuropathological changes in the absence of microglia, with atrophy, neuron loss, vascular disturbances, macroglial dysregulation, and severe calcifications all detected in this region. Thalamic calcification formation, which often occurs with normal ageing, is dramatically accelerated in Csf1rΔFIRE/ΔFIRE brains but can be prevented via transplantation of wild-type microglia. Our results indicate that lifelong absence of microglia results in an age-related neurodegenerative condition that can be prevented by the transplantation of healthy microglia.

Bestard-Cuche, N., & Munro, D. (2024). Microglia protect against age-associated brain pathologies - all scRNAseq datasets [Data set]. Zenodo. https://doi.org/10.5281/zenodo.11198851