Extended Data Fig. 9: Proteomic and metabolomic changes in response to LRRC58 depletion in mouse liver.

(a) Scheme for investigating liver cysteine, cholesterol, total triglycerides (TG), and bile acid levels in response to liver-specific LRRC58^KD in vivo. Created in BioRender. Xiao, H. (2025) https://BioRender.com/zub3s1i. (b) Transcript abundance of LRRC58 in scramble (scr) compared to LRRC58^KD in the liver. n = 11 male mice, LRRC58^KD n = 12 male mice. (c) Transcript abundance of LRRC58 in scramble (scr) compared to LRRC58^KD in other tissues. n = 4 male mice. (d, e) Hepatic taurine and hypotaurine abundance in scramble (scr) compared to LRRC58^KD mice. Scramble (scr) n = 11 male mice, LRRC58^KD n = 12 male mice. (f) Schema of stable isotope tracing using labeled ¹³C₆¹⁵N₂ -cystine to evaluate taurine flux in vivo following liver-specific LRRC58^KD. Created in BioRender. Xiao, H. (2025) https://BioRender.com/1yuzp7v. (g) Transcript abundance of Lrrc58 in scramble (scr) compared to LRRC58^KD in the liver of mice used for L-cystine (¹³C₆ ¹⁵N₂) tracing experiments. n = 9 male mice, LRRC58^KD n = 10 male mice. (h) Abundance of fatty acid species in the liver of scramble (scr) compared to LRRC58^KD mice. Scramble (scr) n = 11 male mice, LRRC58^KD n = 12 male mice. (i) Comparison of taurochenodeoxycholic acid, tauro-beta-muricholic acid, and taurocholic acid abundance in scramble (SCR) compared to LRRC58^KD, and LRRC58^KD + CDO1^KD primary hepatocytes. n = 6 cell. (j) Cholesterol levels in scramble (scr) compared to LRRC58^KD, and LRRC58^KD + CDO1^KD primary hepatocytes. n = 4 cell. (two-tailed Student’s t-test for pairwise comparisons in b-e & g-j). Data presented as mean ± s.e.m.

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