Panel A shows a dot plot of M Y C T 1 gene expression specific to the endothelial lineage, with selected markers of endothelial cells and other major human cell types. Panel B presents another dot plot of M Y C T 1 expression across different human endothelial and mural cell subsets, highlighting higher levels in arterial and capillary endothelial cells. Panel C illustrates the generation of a conditional M Y C T 1 deletion mouse model. Panel D depicts the M y c t 1 e c K O mouse model, with methods detailed elsewhere. Panel E shows R T-q P C R results for M y c t 1 and C d h 5 transcripts using lung m R N A from wildtype and M y c t 1 e c K O mice, indicating efficient deletion of M y c t 1 in adult endothelial cells. Panel F is a line graph demonstrating that M y c t 1 ablation prevents age-associated weight gain in mice, with statistical significance noted. Panel G presents a vertical bar graph quantifying organ weight to body weight ratio relative to wildtype mice, showing no significant effect of M y c t 1 ablation on organ size. Panel H shows a bar graph quantifying tibia length relative to wildtype mice, indicating no significant effect of M y c t 1 ablation on bone length. Panel I is a heatmap representing R T-q P C R data for browning markers in white adipose tissue (W A T) and brown adipose tissue (B A T), with B A T used as a positive control. Panel J presents a bar graph quantifying fat pad weight to body weight ratio relative to wildtype mice under high-fat diet conditions, showing significant reductions in fat pad weights in specific regions for M y c t 1 e c K O mice.
Pan-endothelial MYCT1 is required for WAT expansion, related to Fig. 1. (A) MYCT1 expression is specific to the endothelial lineage. Dot plot representation of MYCT1 expression, selected markers of ECs, and other major human cell types. Dataset by Barnett et al. (2024). (B)MYCT1 expression is pan-endothelial with higher levels in arterial and capillary ECs. Dot plot representation of MYCT1 expression and selected markers of human endothelial and mural cell subsets (Barnett et al., 2024). (C) Generation of a conditional Myct1 deletion mouse model. (D)Myct1ecKO mouse model. See Materials and methods for details. (E)Myct1 is efficiently deleted in adult ECs. RT-qPCR for the indicated transcripts using lung mRNA from long-term monitored wild-type or Myct1ecKO mice. n = 3–9 mice per genotype; mean ± SD; multiple Mann–Whitney tests, P = 0.003 (*) for Myct1 and P > 0.05 for Cdh5. (F)Myct1 ablation prevents age-associated weight gain. n = 10 male mice per genotype; mean ± SD; two-way ANOVA with Tukey’s multiple comparisons test, P = 0.0403 (*). (G)Myct1 ablation does not affect organ size. Quantification of organ weight to body weight ratio relative to wild-type mice. n = 5 mice per genotype; mean ± SD; multiple Welch’s t tests, P > 0.05. (H)Myct1 ablation does not affect tibia bone length. Quantification of tibia length relative to wild-type mice. n = 7–9 mice per genotype; mean ± SD; Mann–Whitney test, P > 0.05. (E–H) Data from the long-term Myct1 deletion experiment. (I)Myct1ecko WAT does not express higher levels of browning markers. Heatmap representation of RT-qPCR for the indicated transcripts. BAT was used as a positive control. n = 5 wild-type WAT, 9 Myct1ecKO WAT, and 4 wild-type BAT. (J) Quantification of fat pad weight to body weight ratio relative to wild-type mice under HFD conditions. n = 5 mice per genotype; mean ± SD; multiple Welch’s t test, P > 0.05 for IsWAT and IsBAT (interscapular fat), P = 0.009 (*) for retroperitoneal, P = 0.033 (*) for gonadal, P = 0.004 (*) for inguinal, and P = 0.016 (*) for mesenteric. Icons used in D were created with BioRender.com and modified in Affinity. BAT, brown adipose tissue; IsWAT, interscapular WAT; IsBAT, interscapular BAT.