Fig. 5. snATAC-seq of brain samples from CHIP carriers reveals that the mutated cells are similar to MG and comprise a large proportion of the microglial pool.
a, snATAC-seq profiles of 187,754 cells from our dataset, the Corces 2020 adult human brain dataset and the Satpathy 2019 human blood dataset. Each dot represents the snATAC-seq profile of one cell and is colored by its assigned cluster. b, snATAC-seq profiles of all cells colored by which donor it originated from. Samples from Corces 2020 and Satpathy 2019 are aggregated and shown in gray and dark gray, respectively. c, Cluster composition of hematopoietic cells in each sample in this study. d, Pseudo-bulk tracks for selected gene loci. The top eight tracks show snATAC-seq coverage of cells from the indicated sample (or aggregated Corces 2020 samples) within cluster C6–MG. Clusters C7–monocyte and C8–DC are also included for visual reference. e, Calculation of the proportion of MG bearing a CHIP mutation in each sample. Error bars depict the simulated 95% confidence interval for percent mutant MG in each sample using n = 106 random samples (see Methods for details). f, Correspondence between the fraction of mutant blood cells and mutant MG for each donor (n = 6). Pearson product-moment correlation coefficient and two-sided P value calculated from a t-statistic based on the correlation coefficient are shown. g, Fraction of MG relative to the total glial pool in occipital cortex samples from CHIP and non-CHIP donors, computed from frequencies of the indicated clusters. Two-sided Wald P value = 0.042 by quasibinomial regression of the cell counts of MG, oligodendrocytes and astrocytes. n = 10 donors. Box plot shows median, first quartile and third quartile. Box plot whiskers show minimum and maximum values, which are capped at a distance of 1.5× (interquartile range) away from the box. The colors in d–g represent the sample name as depicted in the box under Fig. 4b. Detailed information for each donor is available in Supplementary Table 14. Samples are unsorted and are taken from the occipital cortex unless otherwise indicated. Ce, cerebellum; P, putamen.