Extended Data Fig. 6: TREM2 is a phagocytic receptor for LC-EVs.
From: An extracellular vesicle-mediated mitochondrial transfer network critical for testosterone synthesis
a, Schematic diagram depicts experimental design. Cx3cr1CreER (Con) or Cx3cr1CreER; Trem2fl/fl (cKO) mice were treated with TAM, and then analysed at indicated time points. b, Quantitative RT-PCR analysis of Trem2 expression in Con or cKO mice 14 days after treatment with TAM (n = 3 mice per group). c, Representative images of testes stained with TREM2 and F4/80 in Con or cKO mice 14 days after injections of TAM (n = 5 mice per group). Scale bars, 5 μm. d, Quantification of TREM2 expression on tMacs (n = 5 mice per group). e, Schematic diagram depicts experimental design. tMacs were sorted from Con or cKO mice, and then co-cultured with mitoD2+ LCs isolated from Cyp17a1Cre; R26mitoD2 mice, respectively. f, Representative images of Con-tMacs and cKO-tMacs co-cultured with mitoD2+ LCs for 24 h (n = 5 biological replicates per group). Scale bars, 5 μm. g, Percentage of tMacs containing mitoD2+ signals (n = 5 biological replicates per group). h, Representative TEM images of testes from Con or cKO mice (n = 4 mice per group). Scale bars, 1 μm. Inset shows boxed regions that are magnified. Scale bars, 200 nm. i, Quantification of the ratio of cristae area to mitochondrial area (n = 80 mitochondria within LCs and LC-EVs from 4 mice for each group). j, Quantification of the number of mitochondria within LC-EVs (n = 4 mice per group, 5 view fields were captured and 2,000 μm2 images were analysed for each mouse). k, Schematic diagram depicts experimental design. Testes tissues from Cyp17a1Cre; R26mitoD2 mice were cultured with vehicle (Con) or TREM2 inhibitor IA9 (IA9) for 48 h before analysis. l, Representative confocal images of testes tissues cultured with Con or IA9. Testes sections were immunostained with F4/80 (n = 4 biological replicates per group). Scale bars, 3 μm. m, Percentage of tMacs containing mitoD2+ signals (n = 4 biological replicates per group). n, The concentrations of testosterone in the supernatant of cultured testes tissue treated with Con or IA9 (n = 5 biological replicates per group). Data are represented by mean ± SEM (b,j), box plots (d,g,m,n), or violin plots (i). Box plots: the box bounds depict the first quartile to the third quartile, with the middle line indicating the median and the whiskers extending to the minimum and maximum values. Significances were determined by Two-tailed Student’s t-test (b,g,j,m), Two-tailed Welch’s t-test (d,n), or Two-tailed Mann–Whitney U-test (i). Schematics in a,e,k created in BioRender. Xia, K. (2026) https://biorender.com/begwixv. Source numerical data are provided.
