Fig. 3: Tm4sf19 is expressed in Trem2+macrophages and TM4SF19 KO reduces HFD-induced recruitment of Trem2+ macrophages in GWAT. | Nature Communications

Fig. 3: Tm4sf19 is expressed in Trem2+macrophages and TM4SF19 KO reduces HFD-induced recruitment of Trem2+ macrophages in GWAT.

From: TM4SF19-mediated control of lysosomal activity in macrophages contributes to obesity-induced inflammation and metabolic dysfunction

Fig. 3

A Experimental strategy of snRNA-seq analysis of HFD-fed TM4SF19 KO mice. B Confirmation of TM4SF19 expression levels in GWAT of NCD or HFD-fed TM4SF19 KO and WT mice by immunoblot analysis (n = 6 mice). C UMAP plot of total 54,960 nuclei isolated from GWAT of WT and TM4SF19 KO mice fed NCD or HFD for 12 weeks. (two replicates per condition). Clusters are colored by cell types: Adipocyte, mesothelial cell (MC), lymphatic endothelial cell (LEC), vascular endothelial cell (VEC), adipocyte progenitor cell (APC), smooth muscle cell (SMC), Lyve1+macrophage (Mac.Lyve1), Trem2+macrophage (Mac.Trem2), Prg4+macrophage (Mac.Prg4), monocyte, dendritic cell (DC), B cell and T cell. D Total cell type composition of NCD and HFD-fed WT and TM4SF19 KO mice in each sample. E Monocyte and macrophage subtype composition in total cell population for each condition (WT NCD, TM4SF19 KO NCD, WT HFD, TM4SF19 KO HFD). The error bar represents mean ± SD (n = 2 mice). F Average Tm4sf19 expression levels of each cell type in WT and TM4SF19 KO mice fed NCD and HFD. G tSNE plots showing in silico pseudotime analysis of monocyte and macrophage subtypes. Cells were colored by cell types (left) and pseudotime (right). The arrows on the left panel show differentiation directionality. H tSNE plots split by NCD or HFD condition. The color indicates the density of cells. I Density plot showing the distribution of cells into Lyve1+macrophage (Mac.Lyve1) path and Trem2+macrophage (Mac.Trem2) path of HFD-fed WT and TM4SF19 KO mice according to pseudotime. J Mac.Lyve1 (left) and Mac.Trem2 (right) gene signature scores in Trem2+macrophage in each condition (WT NCD, TM4SF19 KO NCD, WT HFD, TM4SF19 KO HFD). ns: p > 0.05. (p-values for mac.Trem2 signature score = 2.03e-36, mac.Lyve1 signature score = 5.98e-22). Data are presented as mean values ± SEM (B) or SD (E). p-values were determined by the unpaired two-sided Student’s t-test (J) and two-way ANOVA followed by Bonferroni post hoc tests (B). Source Data are provided as a Source Data File.

Back to article page