Fig. 5: The LOAD-risk allele of PICALM causes LD accumulation and lysosomal dysregulation.
From: PICALM Alzheimer’s risk allele causes aberrant lipid droplets in microglia
a, Immunofluorescence staining of LD (BODIPY+) in iMGs carrying risk or non-risk allele. C1, clone 1; C2, clone 2. Scale bars, 50 µm. b,c, Quantification of a shows increased LD (BODIPY+) puncta density (b) and area per cell (c) in LOAD-risk-allele iMGs (versus non-risk). Each data point represents a single-well measurement from 1 experiment; for each donor line (CD04 and CD09) and each condition (risk and non-risk), data are from 2 clones, collected from 2 independent experiments each with 3 wells of differentiations (n = 12). d, Dysfunctional lysosomes may contribute to LD accumulation in LOAD-risk-allele iMGs. The log2[FC] of known lysosomal genes and LD suppressor genes in LOAD-risk-allele iMGs or with iMGs with PICALM-CRISPRoff (versus non-risk) is shown. e, Representative images of iMG staining for LD (BODIPY+) and lysosomes (LysoTracker+) in iMGs carrying PICALM non-risk or risk alleles. Scale bars, 50 µm. f,g, Quantification of e for lysosome puncta per iMG (f; LysoTracker+) and colocalized lysosome–LD puncta per iMG (g; BODIPY+LysoTracker+). Each data point represents a single-well measurement from one experiment; for each donor line (CD04 and CD09) and each condition (risk and non-risk), data are from 2 clones, collected from 2 independent experiments each with 3 wells of differentiations (n = 12). In all comparisons, an LMM was used to test the fixed effect of risk allele, with the experimental round and clone identity as nested random factors; two-sided test, nominal P values are shown. *P < 0.05; **P< 0.01; ***P < 0.001. Data are mean ± s.e.m.
